Autologous Stem Cell Transplantation In Pts Research Articles

Long-term outcomes after cardiac transplantation in AL amyloidosis.

7572 Background: Systemic AL amyloidosis can lead to progressive multi-organ dysfunction including advanced heart failure which may require orthotopic heart transplantation (OHT). Hematologic outcomes of AL amyloidosis post-OHT are not well described. Methods: We report outcomes for patients with AL amyloidosis with cardiac involvement post-OHT from Nov 2008 - Jun 2023 at Vanderbilt University Medical Center. Hematologic response was graded per the ISA guidelines. Results: Fourteen pts underwent OHT of whom 13 had lambda light chain disease. Three (21%) pts had isolated AL amyloidosis (AL) without myeloma (MM), while 11 (79%) also had MM: 6 with bone marrow plasma cells (BMPCs) 10-19% (AL-PCMM-10) and 5 with BMPC ≥20% (AL-PCMM-20). One each with AL-PCMM-10 and AL-PCMM-20 had lytic lesions (AL-CRAB). Median age at OHT was 55.5 yrs (range 37-74). Median time from diagnosis to OHT was 18 mo (range 3-62). Five (35%) pts had biopsy-proven extracardiac amyloid involvement. Median difference in serum free light chains at first evaluation was 70 mg/dL (range 9-289). Three pts were Mayo 2012 stage II, 4 stage III, and 7 stage IV. Four pts had t(11;14) and 1 had 1q gain. Ten (71%) pts received triplet therapy (VCd or VRd) and 3 (21%) received quadruplet therapy (Dara-VCd or Isa-VCd) pre-OHT. Six (43%) pts had autologous stem cell transplantation (ASCT); 1 pre-OHT and 5 post-OHT. Of ASCT pts, 1 pt achieved CHR, 1 VGPR, 2 PR, and 1 had PD pre-ASCT. Pre-OHT, 4 pts achieved CHR, 6 VGPR, 3 PR, and 1 had PD. Eleven pts (79%) received maintenance therapy post-OHT (5 proteosome inhibitors, 6 anti-CD38). At last follow-up, 8 pts were in CHR, 3 in VGPR, 1 in PR, and 2 had PD. Four (29%) pts died post-OHT: 2 from AL recurrence (1 each with AL and AL-PCMM-10), 1 from cardiac allograft vasculopathy (AL-CRAB), and 1 from renal failure (AL-CRAB). Three (21%) pts had hematologic relapse 5, 21 and 48 mo post-OHT, and of those, 2 had recurrent cardiac amyloid in graft 37 and 71 mo post-OHT. Of those with hematologic relapse, 2 had AL-PCMM-10 and 1 had AL. One pt had post-transplant lymphoproliferative disorder 126 mo post-OHT, requiring treatment. Median follow-up and survival of the cohort post-OHT was 2.25 yrs (range 0.5-13.8). Conclusions: In this single-center analysis of pts undergoing OHT for cardiac AL amyloidosis, we demonstrate feasibility of excellent long-term outcomes, in predominantly high-risk AL pts where majority harbored high-risk disease with MM overlap, either by AL-CRAB or AL-BMPC. Induction alone led to ≥VGPR response in 10 (71%) pts pre-OHT and further therapy deepened this to 11 (79%) pts. Both AL-CRAB pts died during follow-up, highlighting the overall poor prognosis in this specific subgroup. In our cohort, non-relapse related mortality was seen in only 2 (14%) pts, demonstrating acceptable post-OHT risk and overall ability to achieve far improved outcomes in the high-risk cardiac AL amyloidosis patient population that otherwise suffers from rapid and universal mortality.

1p and 1q: Partners in crime in multiple myeloma.

7571 Background: Cytogenetic abnormalities in multiple myeloma (MM) highly influence the disease course, response to treatment and survival. Trisomies and immunoglobulin H chain translocations are primary CA while del(17p), gain(1q), del(1p) among others are secondary CA. Gain (3 copies) and amplification (>3 copies) 1q have been recognized as adverse prognostic markers and incorporated into the second revision of the International Staging System (R2-ISS). However, the role of del(1p) is less well defined, especially in the era of novel therapies. We aimed to analyze the outcomes of newly diagnosed MM (NDMM) patients with chromosome 1 abnormalities, mainly del 1p, treated with autologous stem cell transplant (ASCT) consolidation at our institution. Methods: We conducted a retrospective study of all NDMM patients who were treated with ASCT from 1/1/2015-2/13/2019 (n=511). High-risk cytogenetics (HRC) were defined by the presence of del(17p), t(4;14), or t(14;16) similar to R-ISS; standard-risk cytogenetics (SRC) were defined as the absence of HRC. Modified HR cytogenetics (mHRC) included gain/amp 1q and/or t(14;20) in addition to HRC, while ultra high-risk (uHRC) included 2 or more mHRC CA. Results: Of 511 pts transplanted, 453 had cytogenetic data at the time of diagnosis. SRC were seen in 353 pts (77.9%), while 100 (22.1%) had HRC, 156 (34.4%) had mHRC, and 43 (9.5%) had uHRC. Thirty-two (7.1%) pts had del(1p) while 105 (23.2%) had gain 1q and 30 (6.6%) had amplification 1q. As expected, compared to SRC pts, pts with HRC, mHRC and uHRC had higher risk of relapse or death. Patients with gain and amp 1q had inferior outcomes in terms of progression-free survival (PFS) (HR 1.35; 95% CI 1.06-1.73, p=0.016), time to next treatment (TTNT) (HR 1.84; 95% CI 1.40-2.42, p<0.001) and overall survival (OS) (HR 1.47; 95% CI 1.06-2.02, p=0.02) compared to those without, consistent with published literature. The median PFS, TTNT and OS from ASCT in pts with gain/amp 1q were 3.17 years (y), 3.95y and 7.13y, respectively, compared to 4.01y, 7.60y and 8.21y in pts without gain/amp 1q. Pts with del(1p) had inferior PFS (median 2.43y versus 3.98y; HR 1.75; 95% CI 1.16-2.64, p=0.008), TTNT (median 2.72y versus 6.17y; HR 1.96; 95% CI 1.22-3.14, p=0.005) and OS (median 4.11y versus 8.38y; HR 2.19; 95% CI 1.34-3.58, p=0.002) from the time of ASCT compared to those without del(1p). Conclusions: In our study of NDMM patients that underwent AHCT, del(1p) at diagnosis was an independent predictor of shorter PFS, TTNT and OS. Despite induction therapy involving novel drugs and ASCT consolidation, patients with del(1p) at diagnosis continue to have inferior outcomes. Larger analyses are needed to validate the prognostic value of del(1p) and investigate its role in predicting outcomes in MM.

Outcomes of Patients with Primary Mediastinal B-Cell Lymphoma Refractory or Relapsed after Frontline R-EPOCH Chemotherapy

Outcomes of Patients with Primary Mediastinal B-Cell Lymphoma Refractory or Relapsed after Frontline R-EPOCH Chemotherapy

Immune Profiling of Newly Diagnosed Multiple Myeloma (NDMM) Treated with Quadruplet Induction and Autologous Stem Cell Transplantation (ASCT) and Comparison with Achievement of Minimal Residual Disease (MRD) Negativity

Background Incorporation of anti-CD38 monoclonal antibodies (mAb) to the triplet backbone of proteasome inhibitor, immunomodulatory agent and corticosteroid has resulted in unprecedented depth of response including MRD negativity in transplant eligible NDMM. While numerous immunological mechanisms of modern quadruplet combinations are proposed, the modulation of the immunoprofiles bone marrow (BM) and peripheral blood (PB) with quadruplet therapy and ASCT are unknown. The baseline as well as longitudinal study of the composition and functionality of the immune microenvironment with treatment may have implications on disease response. Methods We prospectively collected clinically annotated patient (pt) samples from a phase II single institution clinical trial in transplant eligible NDMM (NCT04991103). Pts received quadruplet combination with daratumumab, bortezomib, lenalidomide and dexamethasone for six cycles followed by MRD adapted deferral of ASCT for pts who achieved MRD<10 -5. Pts deferring ASCT received three additional cycles of consolidation followed by maintenance. Pts who did not meet threshold for ASCT deferral received ASCT followed by maintenance therapy per protocol. We collected paired PB and BM samples at the time of screening (SCN), post-induction (I), and post-consolidation/ASCT (C). We purified and biobanked viable PB mononuclear cells (PBMCs). We thawed PBMCs, treated with FcR blocking Ab, stained with fluorochrome-labeled antibodies and a live/dead fixable stain, and then analyzed using the FACSymphony A5 SE flow cytometer. We identified immune cell subsets in PBMCs using FlowJo v10.2. We report data as percentage of each population within total live PBMCs. Results We collected 48 samples from 8 pts at three timepoints (SCN, I and C) and performed initial immunophenotyping analysis on the PBMCs. We observed no significant changes over time in the frequencies of peripheral CD45 +, CD3 +, NK T cells, monocytes or dendritic cells (not shown). We noted decreased frequencies of multiple B cell subsets, including naïve, transitional, memory and double negative cells (not shown), as well as CD56 +CD16 + NK cells (Fig. panel A) post-induction with no recovery following consolidation . While the frequencies of CD3 + T cells did not change with time, we observed a shift in the CD4:CD8 ratio, with an increase in the proportion of CD8 + T cells post-consolidation (Fig. panel B). Within the post-consolidation CD8 + T cell compartment, we noted increased frequencies of cells that presented with senescent (PD1 negCD57 +), exhausted (PD1 +CD57 neg) or anergic (PD1 +CD57 +) profiles. Consistent with this, the frequencies of terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 + T cells increased at consolidation (Fig. panel C) and many of these cells exhibited an anergic profile (CD57 +PD1 +, Fig. panel D). Comparison of the baseline immune profiles and MRD levels post-induction revealed that the pt attaining MRD<10 -5 had the highest frequency of-NK cells as well as proportionally higher T CM/T EM and lower TEMRA/T Naive cells at diagnosis. This subject was able to defer ASCT per protocol and subsequently exhibited the lowest frequency of CD8 + TEMRA with an anergic phenotype (PD1 +CD57 +) post quadruplet consolidation. The subject with the least response to quadruplet induction and highest MRD post-induction had a high proportion of CD8 + T cells with an exhausted phenotype (PD1 +CD57 neg) at screening. Conclusion This is the first longitudinal analysis comparing MRD levels to the immune profiles of PB and BM cells derived from a cohort of NDMM patients prospectively treated with quadruplet induction and ASCT. We conclude that quadruplet induction negatively affects the NK cell and B cell compartment during induction and these compartments do not rapidly recover in the immediate post-transplant period. ASCT post quadruplet therapy is associated with preferential expansion of the effector CD8 + T cell compartments, including terminally differentiated TEMRA cells, which express markers associated with T cell exhaustion and anergy. Additional studies evaluating BM immune profile and T cell exhaustion are ongoing and shown at the meeting.

Real-World Results of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: A Multi-Institutional Report from the Canadian Myeloma Research Group (CMRG) Database

INTRODUCTION Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients (pts) as part of initial therapy. In Canada, fit younger pts are typically offered ASCT; selected centers offer tandem ASCT to high-risk (HR) pts; and current standard practice involves continuation of maintenance (maint) therapy until disease progression, which is facilitated by public funding for lenalidomide (len) in this setting. Using our national database, we examined the details and outcomes of ASCT performed as part of initial therapy in eligible Canadian MM pts. Methods The Canadian Myeloma Research Group database (CMRG-DB) contains both legacy and ongoing prospective data and can track and characterize real-world outcome of pts treated at 17 major Canadian institutions. All pts who received an ASCT as part of initial MM therapy between 01/Jan/2007 to 31/Dec/2021 were included. Progression-free survival (PFS) was calculated from the time of first ASCT until disease progression, death due to any cause or last follow up, whichever comes first, while overall survival (OS) was defined as the time from ASCT to the date of death or last follow up. Results 3821 pts underwent ASCT as frontline therapy and were included in the analysis. Median age was 61 (range 26-77) years, 15.2% had a creatinine > 177 umol/L and 18% had HR FISH [del17p, t(4;14) and t(14;16)] (FISH was unknown/missing in 50% of pts). The majority (82%) received bortezomib (btz)-based induction; this consisted of CyBorD in 72% with rates of ≥PR (≥VGPR) of 92% (60%). Only 1.6% received a proteasome inhibitor (PI) + len; rates of ≥PR (≥VGPR) were 96.5% (63.2%) in this subgroup. Median time to ASCT from start of induction was 5.6 months (mos). A second induction regimen, including len in 78.5%, was administered to 376 pts for suboptimal response/progression on first induction. The ≥PR (≥VGPR) rates in these 376 pts was 72.9% (35.4%) with a median time from start of second induction to ASCT of 4.2 mos. Tandem ASCT was performed in 314 pts, primarily in HR pts (64%). In HR FISH pts, the median PFS (mPFS) for single vs tandem ASCT was 25.1 vs 35.4 mos (p 0.018) and median OS (mOS) 91.5 vs 84.4 mos (p 0.048), respectively. For those without HR FISH, mPFS and mOS for single vs tandem ASCT were, respectively, 46.5 vs 33.8 mos (p <0.001) and 158.6 vs NYR (p <0.001). After ASCT, only 205 (5%) pts received consolidation that consisted of a PI + len in 93.2%. However, 2060 pts (53.9%) received post-ASCT maint (len +/- steroids in 63.1%, btz +/- steroids in 2.1 %, len + btz +/- steroids in 1.7%, other PI +/- steroids in 1.6%, len + other PI +/- steroids in 5.7 % and thalidomide +/- steroids in 8.5%). The mPFS and mOS for all pts was 35.4 mos (95% CI 33.7-37.3) and 125 mos (95% CI 120-138) from first ASCT. Table 1 summarizes the mPFS and mOS according to treatment. Those given a second induction regimen had significantly inferior outcomes (mPFS 27.9 vs 36.2 mos [p 0.001]; mOS 118 vs 126 mos [p 0.011]), although the use of maintenance led to comparable results regardless of number of induction regimens (mPFS 55.3 vs 51.1 mos [p 0.11]; mOS 158.6 vs not yet reached (NYR) [p 0.13]). Consolidation pts had a better mPFS (55.3 vs 34.4 mos [p 0.001]), but no significant gain in mOS (p 0.065). The mPFS and mOS were 48.8 vs 24.5 mos and 159 vs 105 mos for the maint vs non-maint cohorts, respectively, when all types of maint were included. For pts receiving len, btz or both (+/- steroids), the mPFS was 53.7 mos vs 48.2 mos vs 43.5 mos, respectively, while the mOS was 159 mos vs NYR vs 115 mos, respectively. Amongst pts receiving such maint, outcomes for pts with HR FISH were compared with those without HR FISH: mPFS was 36.6 mos vs 55.2 mos and the mOS was 97.4 mos vs 164.4 mos, respectively. CONCLUSIONS This large study demonstrates that the integration of btz and len into the transplant sequence produces a mOS of ≥10 yrs in most ASCT pts in the real-world setting. Our observations highlight the contribution of post-ASCT maint, particularly len given until progression, when used in multiple pt groups including those with and without HR, as well as those requiring a second induction regimen. Nevertheless, HR pts require additional strategies to optimize results. Further analyses to assess the relationship of pt characteristics, specific treatment details and outcomes are in progress. These results serve as Canadian benchmarks for comparison with newer approaches that combine immunotherapy with ASCT as initial therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluating Risk Factors and Outcomes For Clostridium Difficile Infection (CDI) In Stem Cell Transplant (SCT) Recipients

IntroductionClostridium difficile infections (CDI) are the leading cause of infectious diarrhea among pts undergoing stem cell transplantation (SCT). Data from large pt samples evaluating the trends, risk factors, hospitalization outcomes are lacking. We have analyzed the Nationwide Inpt Sample (NIS) database to evaluate the trends in the incidence and the impact of CDI on hospitalization outcomes among SCT recipients. MethodsWe used the NIS database to obtain the hospitalization data for primary procedures of autologous and allogeneic SCT between 01/2001 until 12/2010. We performed separate multivariate logistic regression analyses to evaluate risk factors of CDI in SCT pts and hospitalization outcomes including length of stay (LOS), in-hospital mortality (IHM) and hospitalization charges. Comorbidites were identified using software that created measures reported by Elixhauser et al. ResultsThe incidence of CDI among transplant pts has remained relatively stable over time (Fig 1), with a higher cumulative incidence of CDI among recipients of allogeneic grafts (allogeneic vs. autologous SCT: 8.29% vs. 5.63%; p<0.001). There was an association between CDI and the presence of multiple comorbidities among autologous SCT pts (p=0.05), and a similar trend was seen in allogeneic transplant pts. Mean LOS (CDI vs. none: autologous 26 vs. 20 days, p<0.0001; allogeneic 42 vs 30 days, p<0.001; respectively), IHM (CDI vs. none: autologous, 4.0 vs. 2.2%, p=0.0003; allogeneic 12.7 vs 9.2%, p=0.0008) and mean hospitalization charges (CDI vs. none: autologous $208,025 vs. $145,250, p<0.0001; allogeneic $367,415 vs $270,366 p<0.0001; respectively) were significantly higher among SCT pts with CDI (Table 1). [Display omitted] Table 1Pt characteristics, multivariate regression models for evaluating risk and outcomes of SCT pts with CDIAutologous SCTAllogeneic SCTCDI (%) (N=3772)SCT patients (%) (N=63202)p-valueCDI (%) (N=3440)SCT patients (N=38066)p-valueMean age (SE)54.3 (0.52)52.02 (0.27)<0.000145.07 (0.64)46.57 (0.38)<0.0098Male2311 (61.3)37038 (58.6)0.15962188 (63.6)21906 (57.6)0.0005White2369 (77.4)26124 (74.3)0.10892199 (77.7)23695 (78)0.847Comorbidities ≥12945 (78)46872 (74.2)0.052607 (75.8)27712 (72.8)0.1073Medicare945 (25.1)12460 (19.8)<0.0001310 (9.0)4111 (10.8)0.183Medicaid330 (8.8)6818 (10.8)0.1161474 (13.8)3996 (10.5)0.0126Private Insurance2320 (61.6)40209 (63.8)0.24832486 (72.4)27601 (72.7)0.8798Mean LOS (SE)*26 (0.71)20 (0.27)<0.0001*42 (1.59)30 (0.68)<0.0001*IHM152 (4.0)1330 (2.1)0.0003438 (12.7)3360 (8.8)0.0008Charge Mean (SE)208025 (8370.6)145250 (4311.3)<0.0001*$367415 (15033)$270366 (11835)<0.0001*Multivariate logistic regression model evaluating risk of CDI in SCT patientsVariableOdds RatioRefp-valueOdds RatioRefp-value≥651.4 (0.987-1.985)Age <40 (Ref)0.19450.637 (0.426-0.953)0.0834Male1.25 (1.054-1.483)Female (Ref)0.01031.351 (1.157-1.576)Female (Ref)0.0001Medicare1.149 (0.878-1.502)Private (Ref)0.04390.85 (0.581-1.244)Private (Ref)0.4605Medicaid0.887 (0.642-1.226)0.76731.269 (0.920-1.749)0.0272No Comorbidities0.831 (0.650-1.063)Comorbidities ≥10.14060.829 (0.672-1.024)Comorbidities ≥10.082 ConclusionsThe incidence of CDI among both autologous and allogeneic SCTs have remained stable over the last decade, with a slightly higher risk among allogeneic SCT pts. CDI was associated with longer hospital stay, higher charges and higher IHM for both autologous and allogeneic transplant pts. While this analysis does not permit us to directly ascribe differences in outcome to CDI alone, these data suggest that CDI has a major morbid impact in the setting of SCT, and provides a rationale for development of more effective approaches for prevention of CDI in these pt populations. Disclosures:Kaufman:Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.Multivariate logistic regression model evaluating hospitalization outcomes in SCT patients with CDI #CDIAbsencePresencep-valueCDIAbsencePresencep-valueLOS >19 days0.382 (0.31-0.466)1.00 (Ref)<0.0001LOS > 27 days0.337 (0.27-0.42)1.00 (Ref)<0.0001Charge > $125,0910.483 (0.40-0.58)<0.0001Charge > $22,60110.487 (0.38-0.67)<0.0001IHM0.68 (0.44-1.06)0.089IHM0.661 (0.50-0.87)0.0037SE: Standard error; *adjusted for age, race, sex, comorbidity and payer status.#Median LOS and charges used as cut-off for hospitalization outcomes

Real World Outcomes of Newly Diagnosed High-Risk Multiple Myeloma Patients Treated at Princess Margaret Cancer Centre: A Retrospective Chart Review

Background: In the era prior to the availability of novel agents, we have previously reported that the median progression-free survival (PFS) and overall survival (OS) of high-risk (HR) multiple myeloma (MM) patients (pts) undergoing a single autologous stem cell transplant (ASCT) was only 9.9 and 18.3 months, respectively (Chang H et al., Bone Marrow Transplant, 36 (2005), 793). The current study expands our experience in newly diagnosed HR pts and focuses on the outcomes in pts treated with single or tandem ASCT.Methods: A retrospective chart review of myeloma pts was conducted based on pt information retrieved from the Princess Margaret Myeloma Database. 245 pts with HR MM diagnosed and treated in our centre from Oct 1998 to Dec 2016 were identified. Survival rates were calculated using the Kaplan-Meier product-limit method and the log rank-statistic was used for comparison of survival curves.Results: Pts were considered HR based on the presence of any one of the cytogenetic features: t(4:14) (71%), t(14:16) (36%), and chromosome 17p deletion (42%). Characteristics at the time of MM diagnosis of the 245 pts identified as HR are summarized in Table 1. The median age was 60.9 years. First-line therapy included the following: tandem ASCT in 86 pts (35%), single ASCT in 84 pts (34%), and no ASCT in 75 pts (31%). Of the 170 pts who underwent single or tandem ASCT, 119 (70%) received maintenance therapy post-ASCT, including 84% of the tandem ASCT pts and 56% of the single ASCT pts.Median follow-up was 29.3 months (range 1.1-123.7). The median PFS from date of diagnosis of all HR pts was 33.1 months [95% CI 29.3-37.0 months], while the median OS was 79.2 months [95% CI 58.3-90.9 months]. Both PFS (p= 0.0003) and OS (p= 0.0011) were significantly affected by first-line therapy with a median PFS of 53.1 vs 32.9 vs 21.8 months and median OS of 88.5 vs 71.9 vs 55.0 months in pts treated with tandem ASCT, single ASCT and no ASCT, respectively. Tandem ASCT pts had improved PFS and OS survival at 1, 2, and 5-years compared to single and non-transplant pts (Fig. 1A & B). Age at diagnosis significantly affected the PFS (p= 0.0003) and marginally affected the OS (p= 0.0748), likely due in part to our policy for the preferential use of fixed-duration non-ASCT as first-line therapy in older individuals (typically ≥70 years of age). On the other hand, serum beta 2- microglobulin levels correlated significantly with OS (p= 0.0023) while the association with PFS was not significant. Among ASCT pts, those who received tandem ASCTs vs single ASCT demonstrated a significantly better PFS (p= 0.0039) and showed a trend for improved OS (p= 0.0707). Amongst pts who received single ASCT, those with maintenance vs no maintenance demonstrated significantly better PFS (p=0.0082). Finally, pts with both t(4:14) and 17p deletion (28 pts) had a significantly decreased PFS (p= 0.0414) and a trend for decreased OS (p= 0.0621) compared to those with only one abnormality (Fig. 1C & D).Conclusions: Although adverse factors such as older age and co-morbidities likely affected the ability to perform 1 or 2 autografts and likely introduced bias into our analysis, our data nevertheless suggest that tandem ASCT is an effective approach in extending PFS and OS among HR MM pts when compared to single transplants or none at all in the real-world setting. Multivariate analysis is underway to further delineate the factors contributing to PFS and OS in HR pts. As in other transplant studies, the PFS is improved in pts who receive maintenance therapy after single ASCT. Efforts should be made to offer newly diagnosed HR MM pts a program that includes tandem transplantation, if feasible, as well as maintenance therapy post-transplant. Pts with “ultra HR” MM, i.e., those with both t(4;14) and 17p deletion, require new innovative approaches. [Display omitted] DisclosuresReece:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Paid expert testimony, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Paid expert testimony, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Otsuka: Research Funding. Chen:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbvie: Honoraria; Amgen: Honoraria. Kukreti:Celgene: Honoraria; Amgen: Honoraria. Prica:Janssen: Honoraria; Celgene: Honoraria. Tiedemann:BMS Canada: Honoraria; Celgene: Honoraria; Takeda Oncology: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Trudel:Janssen: Research Funding; Amgen: Consultancy, Honoraria; Astellas: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Honoraria; GlaxoSmithKline: Research Funding.

Prognostic Effect of Decline in Pulmonary Function Testing after Autologous Stem Cell Transplantation

BackgroundLarge retrospective analyses of patients (pts) undergoing allogeneic stem cell transplant have demonstrated association between decline in pulmonary function and increases in mortality. There is a paucity of similar evidence for pts undergoing autologous stem cell transplant (ASCT). We conducted a retrospective study of lymphoma pts undergoing ASCT to investigate association between early post-transplant decrease in pulmonary function tests (PFTs) and mortality. We hypothesized that decreases in pulmonary function in the early post-transplant period in ASCT pts would be associated with greater risk of overall and non-relapse mortality.Methods and PatientsWe identified 853 lymphoma pts age ≥18 years who underwent ASCT at Cleveland Clinic between 2000-2016 and had completed both pre- and post-ASCT PFTs. Two PFT values were assessed: percent predicted FEV1 and DLCO. Endpoints for the study included overall survival (OS) and non-relapse mortality (NRM). Decrease from pre- to post-ASCT for each was defined as ≤5%, 5.01-10%, or >10%. Variables associated with decrease in PFTs were identified with Cochran-Mantel-Haenszel trend tests. Risk factors were identified with Cox analysis (OS) or Fine and Gray regression (NRM); results are presented as hazard ratio (HR) and 95% confidence interval (CI).ResultsThe study cohort was predominantly male (63%) and Caucasian (92%) with a median age of 54 years (range 19-78). Primary diagnosis included Hodgkin lymphoma (19%) and non-Hodgkin lymphoma: B cell low-grade (16%) and high-grade (57%), and T cell (8%). The majority had advanced stage disease (79%), received <3 prior chemotherapy regimens (74%), no prior radiation (77%) and were never smokers (56%). Prior bleomycin (23%) and brentuximab (2%) exposure was low. Busulfan, etoposide and cyclophosphamide was the preparative regimen in 98% of pts. Median time to neutrophil and platelet engraftment were 10 and 15 days respectively. At a median follow up of 64 months (range 3-208) 62% of our cohort was alive and 43% had relapsed. Pre-ASCT PFTs were performed at a median of 51 days (range 9-205) prior to transplant. Median pre-transplant FEV1 and DLCO were 93% and 75% of predicted respectively when corrected for anemia. Post-transplant PFTs were obtained at a median 43 days post-transplant (25-92). Decreases in FEV1 of ≤5%, 5.01-10%, and >10% were observed in 71%, 15%, and 15% of pts, respectively. Corresponding decreases in DLCO were 70%, 11%, and 20%, respectively. Decrease in FEV1 was associated with male gender, intermediate risk disease, chemo-mobilization, and increased days of apheresis. Decreasing DLCO was associated with Caucasian ethnicity, and advanced stage. Pts with FEV1 decline were more likely to experience increased hospital stay and readmission within 100 days post ASCT. Prior bleomycin use did not impact PFTs or outcomes.For our cohort, 5- and 10-year NRM were 10% and 15% respectively; 5- and 10-year OS were 63% and 53% . In univariate analysis, pts with >10% FEV1 decrease had significantly worse NRM (HR 2.07, 95% CI 1.27-3.38, p=0.004) (Figure 1) and OS (HR: 1.42, 95% CI 1.07-1.89, p=0.016) (Figure 1a) than those with ≤5% decrease; pts with 5.01-10% FEV1 decrease had similar NRM (HR 1.58, 95% CI 0.92-2.72, p=0.10) and OS (HR 1.15, CI 0.85-1.57, p=0.37) to those with ≤5% decrease . Only minimal decreases in DLCO (0.01-5%) impacted NRM (HR: 0.23, CI = 0.06 - 0.95, p=0.042), while >5% decline had no significance on NRM or OS. In multivariable analysis, >10% FEV1 decrease retained significance for NRM (HR 1.96, 95% CI 1.20-3.20, p=0.008), with a trend towards poor OS (HR 1.33, CI 0.99-1.77, p=0.06) (Figure 2). Pts with 5.01-10% decrease had marginally higher risk of NRM (HR 1.55, 95% CI 0.90-2.66, p=0.11) but not OS (HR 1.14, 95% CI 0.83-1.55, p=0.42). Other prognostic factors for increased NRM included older age, chemo-mobilization, and more days of apheresis. These three were also prognostic for worse OS along with more prior chemotherapy and high-risk disease.ConclusionDecrements of FEV1 >10% in the early post-transplant period are associated with increased NRM and inferior OS in lymphoma pts undergoing ASCT. Greater decrease in DLCO was not associated with decreased OS or increased NRM. Further stratification and analysis of the population with large decreases in pulmonary function may help with development of screening and interventional strategies in high risk pts. [Display omitted] DisclosuresGerds:Incyte: Consultancy; CTI BioPharma: Consultancy. Majhail:Sanofi: Honoraria; Anthem, Inc.: Consultancy.

Poor Graft Function Following Autologous Stem Cell Transplant (ASCT): A Retrospective Analysis over Two Decades at a Transplant Center

Introduction: A limited knowledge exists regarding the incidence and risk factors of poor graft function (PGF) following ASCT. There are multiple factors related to either quality of infused hematopoietic cells such as inadequate numbers or poor viability, or host factors such as chemotherapy induced stromal damage, bone marrow fibrosis, post-transplant infections, relapse, or drug-induced myelosupression which can contribute to development PGF in ASCT recipients.Methods: Quality of engraftment of 1,162 patients (pts) who received ASCT at a single institution from 01/1996 to 08/2016 were retrospectively reviewed. PGF was defined as: platelet count ≤50,000/μL, Hgb ≤8 g/dL, absolute neutrophil count ≤1,000/mm3 or requirement of transfusions of blood products starting at 30 days post ASCT. Pts who received more than one ASCT, and those lost to follow-up within one-year of ASCT were excluded from analysis.Results: Out of 1162 pts, there were 666 males (57.3%) and 496 females (42.7%) with a median age of 58 years (14-81 years). The median follow-up time was 21.5 months (1-116 months). Multiple myeloma was diagnosed in a majority of patients (682, 58.7%).146 pts (12.6%) had diffuse large B-cell lymphoma, 70 pts (6%) had mantle cell lymphoma, and 138 pts (11.9%) had Hodgkin's Lymphoma. Relapse was found in 23/239 (9.6%) of pts at a median time to relapse at 117 days. 17/239 (7%) patients died of other causes. 239 pts (21%) without relapse were found having PGF at Day 30 after ASCT (Fig 1). Out of these 239 pts, 194 (81.2%) had inadequate platelet recovery, 42 (17.6%) had inadequate recovery of both Hgb and platelets, and 3 (1.2%) had inadequate recovery of hemoglobin alone. There were no pts with inadequate neutrophil recovery at day 30. Of the 239 pts who had PGF at 30 days, 111 (46.4%) continued having PGF at day 90 after ASCT, with poor platelet engraftment in 100/111 (90%) pts, and poor Hgb and platelet recovery in 11/100 (10%) pts. At 6 months after ASCT, 54 patients (5%) were still showing PGF with inadequate platelet recovery in 49/54 (91%) pts and poor Hgb and platelet recovery in 5/54 (9%) pts. At 12 months post ASCT, 17 pts (1.4%) had PGF with inadequate platelet engraftment in all 17 pts. Pts with PGF received median stem cell dose (SCD) of 4.5X106 CD34/kg (range 1.4-10.5X 106 CD34/kg). Only 5/239 pts with PFG received SCD < 2X106 CD34/kg and only 2/5 pts had a PGF lasting > 6 months. No pts received cell products with cell viability <85%. Clinical and laboratory characteristics of patients with PGF lasting 30 days, 90 days, 6 months, and one year were compared by age, sex, race, weight, CMV status, conditioning regimen, and pre-transplant white count, hemoglobin/hematocrit, and platelet count. Among all groups, factors found not to influence PGF included age (53.5-54.3 years), conditioning regimen, transfusion dependence (21.8%-27.0%), pre-transplant white blood cell count (4.2-6.2/mm3), pre-transplant platelet count (116-138/mm3), or race. Predisposing factors for prolonged PGF included past CMV infection (p<0.01), pre-transplant weight (p<0.01), pre-transplant hemoglobin (p<0.05), and pre-transplant hematocrit (p<0.05).Conclusion: PGF remains a common complication after ASCT in pts without relapsed disease even if adequate dose and viability of stem cells are infused. Inadequate platelet recovery is the most frequent manifestation of PGF which can persists longer than 6 months. CMV status, weight, and pre-transplant hemoglobin/hematocrit were predisposing factors for development of prolonged PGF lasting more than 3 months. [Display omitted] DisclosuresCogle:Celgene: Other: Membership on Steering Committee for Connect MDS/AML Registry. Norkin:Celgene: Honoraria, Research Funding.

Utilization of Cryopreserved Stem Cell Re-Infusion without Conditioning Chemotherapy in Primary and Secondary Autologous Graft Failure Following an Autologous Stem Cell Transplant in Multiple Myeloma

<h3>Introduction</h3> Primary (1°) and secondary (2°) graft failure are a rare but serious complication in autologous stem cell transplant (ASCT) for multiple myeloma (MM) for which reinfusion of cryopreserved autologous stem cells (i.e. stem cell boost) can be performed in the absence of conditioning chemotherapy. However, the efficacy of this approach and kinetics of engraftment without conditioning chemotherapy is unknown. <h3>Methods</h3> Retrospective analysis was performed of all patients (pts) with MM who experienced 1°graft failure (absence of initial donor cell engraftment with peripheral blood ANC <0.5 × 109/L and platelets <20 × 10 9/L by day +21) or 2°graft failure (initial engraftment and subsequent loss of graft with decrease in ANC to <0.5 × 10⁹/L and platelets <20 × 10⁹/L) after ASCT. We looked at pts who received a stem cell (SC) boost without conditioning chemotherapy and abstracted pre-transplant laboratory data, SC engraftment kinetics and pertinent clinical findings from the EMR. <h3>Results</h3> Between 1/1/2003 and 9/30/2018, 21 pts received SC boosts; 18 patients met inclusion criteria. At time of ASCT, median age was 62 years (range: 44-74); 56% female, median neutrophil count was 3.96 × 10⁹/L (IQR 2.5–4.6), median platelet count was 226 × 10⁹/L (IQR 194-380) and bone marrow evaluations demonstrated no dysplasia or atypical genetics. 9 pts were mobilized with growth factor only (i.e. G-CSF); 8 received chemomobilization (G-CSF & cyclophosphamide), 2 pts required Plerixifor and median apheresis sessions was 2 (range 1-6). Most pts collected ≥3 × 10⁶ SC in 1 apheresis. Median time from SC collection to ASCT was 8 days (IQR 6-18) for upfront ASCT pts (n=15) and in delayed ASCT pts (n=3), the range was 214 to 3205 days. 16 pts (90%) had high dose melphalan only conditioning, 1 pt had Ibritumomab tiuxetan and another had 153-Samarium-EDTMP added to high dose melphalan. The median ASCT dose was 4.63 × 10⁶ cells/kg (IQR 3.7-6.51). SC boost details are described in table 1. There was no association between neutrophil or platelet count at mobilization or SC dose with engraftment failure by χ² analysis. <h3>Conclusion</h3> This is the only report on the kinetics and outcomes for stem cell boost without conditioning chemotherapy in MM following 1° or 2° graft failure. All pts engrafted both platelets and/or neutrophils soon after SC boost providing evidence that this is an effective procedure in management of patients with either 1° or 2° autologous graft failure.

Outcomes of Autologous Stem Cell Transplant (ASCT) in Patients with t (11;14) Multiple Myeloma(MM)

<h3>Introduction</h3> MM is a clonal disorder of malignant plasma cells. Standard of care for newly diagnosed MM is induction with triplet regimen chemotherapy followed by ASCT. Patients are stratified based on cytogenetic analysis as being high risk and standard risk. t(11;14) comprises ∼ 15-20% of newly diagnosed MM, making it the most common translocation. t(11;14) has been classified as standard risk. However, it is now increasingly being considered as intermediate risk, conferring inferior outcome compared with standard-risk MM.(Walker, Wardell et al. 2012) <h3>Methods</h3> We performed a retrospective analysis of 806 pts with newly diagnosed MM who underwent ASCT at our institution. Pts were stratified as high risk in the presence of t(4;14), t(14;16), gain 1q or del17p.by FISH. PFS and OS rates were estimated using Kaplan-Meier method. Log-rank tests were used to compare the PFS and OS between the two groups. The Cox proportional hazard models were used to estimate the hazard ratios (HR). <h3>Results</h3> Among 806 patients, 156 pts (19.4%) were positive for t(11;14). 81.5% of pts were 65 yrs or younger, and 59% were males. There were no significant differences in pt characteristics (see table) Median PFS from ASCT in pts with t(11;14) was 3.0 yrs (95% CI: 2.3-4.3) vs. 3.3 yrs (95% CI: 2.8-3.8) in those without t(11;14)[HR=1.03, 95% CI: 0.82-1.29, p=0.81. There was no statistical difference in OS from ASCT [HR of 0.97 (95% CI: 0.70-1.33, p 0.84)]. 5 yr PFS rate was 37% for pts with t(11;14) & 53% in pts without. 5 yr OS rate was 65% for pts with t(11;14) & 66% for those without. <h3>Conclusion</h3> t(11;14) is a common cytogenetic abnormality in MM. According to our analysis, there is no significant difference in outcomes following ASCT in both high risk and standard risk subgroups. t(11;14) MM is predicted to be BCL-2 dependent and the use of BCL-2 inhibitors in induction or post-ASCT maintenance is an attractive option to improve outcomes.

Second Autologous Transplantation in Multiple Myeloma with Renal Dysfunction

Introduction Autologous stem cell transplant (ASCT) as a salvage option in patients (pts) with late relapse (≥18 months after upfront ASCT) represents an effective therapy and can prolong response in Multiple Myeloma (MM). Presence of comorbidities such as renal dysfunction can limit treatment options and impact ASCT eligibility. Efficacy and safety data supporting a second ASCT in pts with renal dysfunction for relapsed disease are limited. Methods All adult pts with MM with renal dysfunction undergoing a non-tandem second ASCT at our institution between January 2006 and January 2019 were identified. Renal dysfunction was defined as pre-transplant creatinine clearance ≤ 60 ml/min. Demographics, disease characteristics, and treatment history were compiled. Relapse free survival (RFS), overall survival (OS), relapse rate, and non-relapse mortality (NRM) outcomes were assessed. RFS durations after both the first and second ASCTs for each pt were compared using a paired log-rank test and corresponding hazard ratios (HR) was estimated using a paired cox proportional hazards regression model through mixed-effects models. Results Thirty six pts with renal dysfunction underwent a second ASCT at our institution. Fourteen pts (39%) had progressive disease (PD) and 9 pts (25%) had very good partial response or better. Median time between first and second ASCT was 57.05 months (18.98-103.25). Conditioning regimens included: ≤140 mg/m2 Melphalan (MEL) (61%; n=22), >140 mg/m2 MEL (28%; n=10) and BEAM (8.3%; n=3). Median length of hospitalization during second ASCT was 18 days (Range, 11-74). Median time to granulocyte and platelet engraftment was 12 (9-16) and 19 (0-61) days, respectively. In hospital events included: treatment-requiring infections in 15 pts (41.7%) and cardiac complications in 5 pts (13.9%). Four pts (11.1%) required intensive/critical care admission. By day 100 (d100) assessment, 30 of 34 surviving pts (83% by ITT) had stable disease or better, and 4 pts (11%) had PD. Twenty pts (58.8%) had an improvement in disease status compared to their pre-ASCT status, while 8 pts (23.5%) maintained their pre-ASCT disease status. Five pts (14%) were readmitted by d100, with 2 pts requiring intensive care. One of 2 pts on dialysis pre-second ASCT became dialysis independent. From second ASCT, median RFS was 1.04 yrs (95% CI, 0.74 to 1.67) and median OS was 3.34 yrs (95% CI, 3.30 to 7.99; median follow up 4.31 yrs); respectively. The cumulative incidence rates for relapse and NRM at 1 yr after second ASCT were 37.1% and 5.6%, respectively. By MVA, light chain MM was associated with higher relapse rate (p=0.03) and lower NRM (p=0.01). Conclusion Our data suggests that second ASCT is well tolerated with low complication /readmission rates in patients with renal dysfunction. Second ASCT as salvage can provide disease control for more than a year for these patients who may have limited treatment options.

Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Effect of Early Recognition of Malnutrition and Targeted Nutrition Support on Clinical Outcomes in Autologous Stem Cell Transplant Patients

Objective Patients (pts) admitted to hospital for autologous stem cell transplant (ASCT) are at risk for malnutrition. American Society for Parenteral and Enteral Nutrition (ASPEN) clinical guidelines recommend nutrition screening and targeted nutrition support for ASCT pts. However, these recommendations are not always followed due to lack of clear evidence of benefit and concern that nutrition support may be associated with increased risk of infection or delayed time to platelet engraftment. We evaluated clinical outcomes in consecutive ASCT pts receiving nutrition assessment and targeted nutrition support based on malnutrition status. Methods A historical control group included consecutive pts admitted for ASCT January 2016 to October 2017 (n = 308). Beginning in October 2017, all ASCT pts (n = 148) received nutrition assessment and intervention to optimize oral intake and were included in the intervention group. Pts diagnosed with malnutrition using Academy of Nutrition and Dietetics-ASPEN criteria and continuing with 15 days after transplant. Pt characteristics included age, Karnofsky performance status (KPS), first vs. subsequent ASCT, and malnutrition risk indicated by a score ≥2 on the validated Malnutrition Screening Tool (MST). Mann-Whitney U tests comparing patients vs. historical controls and logistic regressions were conducted using SPSS (version 25), with p Results Forty-nine pts (33%) met criteria for EN/PN, 40 of whom (82%) received one or both interventions. One pt received EN alone, 37 PN alone, and two EN + PN, for a mean duration of 9.05 days. Pts in the intervention group had lower odds of prolonged LOS (OR = 0.484, 95% CI: 0.259-0.906) and CLABSI (OR = 0.259, 95% CI: 0.073-0.925) in models controlled for age, KPS, first vs. subsequent ASCT, and MST score, with no difference in days to platelet engraftment (p = 0.987). No pt receiving PN or EN was diagnosed with CLABSI. ICU transfer and 30 day readmission rates did not differ between groups Conclusion Identifying malnutrition, optimizing oral intake and providing early, targeted nutrition support to ASCT pts can improve clinical outcomes.

The IMWG Frailty Score and Age Can be More Effective Than Clinical Judgement in the Selection of Elderly Patients with Newly Diagnosed Multiple Myeloma Who Can Benefit from an Intensive Treatment Approach with High Dose Melphalan and Autologous Stem Cell Transplantation

The IMWG Frailty Score and Age Can be More Effective Than Clinical Judgement in the Selection of Elderly Patients with Newly Diagnosed Multiple Myeloma Who Can Benefit from an Intensive Treatment Approach with High Dose Melphalan and Autologous Stem Cell Transplantation

The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study

The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study

Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Classic Hodgkin Lymphoma: Part 3 (Concurrent Dosing) Results and Updated Progression-Free Survival Results from Parts 1 and 2 (Staggered Dosing)

Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Classic Hodgkin Lymphoma: Part 3 (Concurrent Dosing) Results and Updated Progression-Free Survival Results from Parts 1 and 2 (Staggered Dosing)

Pattern of First Relapse in Multiple Myeloma (MM) Patients (Pts) after a Cybord Induction Regimen and Autologous Stem Cell Transplantation (ASCT): Impact of Maintenance Therapy in the Real-World Setting

IntroductionMaintenance therapy after first-line ASCT improves outcomes, although virtually all pts eventually relapse. The pattern of first relapse shows significant heterogeneity. The literature is scarce about the impact of maintenance on the pattern of relapse and about predictors of a more aggressive or indolent relapse course. Our objectives were, in a cohort of transplant-eligible MM pts treated with a CyBorD induction regimen followed by ASCT as part of first-line therapy, to describe the pattern of first relapse, to determine if patterns differ between pts with and without maintenance and to identify predictors for patterns of first relapse, early relapse, PFS, OS and OS after relapse in the real-world setting.MethodsInclusion criteria were MM pts who received at least 2 cycles of induction with a CyBorD regimen with their induction regimen start date from January 2007 to December 2012. Pts then underwent single (126) or tandem ASCT (10) in first-line. Primary refractory disease was excluded. Charts were retrospectively reviewed for descriptive and univariate analysis. The pattern of relapse was categorized as biochemical, clinical, clinical with extramedullary disease or clinical with plasma cell leukemia.ResultsMedian follow-up of the 136 pts was 43.4 months (mos). Pt and first-line treatment characteristics are presented in Table 1. Most pts presented with anemia and bone lesions. The maintenance (n= 82; lenalidomide= 84%, thalidomide= 13%, lenalidomide and bortezomib= 2%) and no maintenance (n= 44) groups were similar, except for fewer pts with high-risk cytogenetics in the no maintenance group (9% vs 19%). All 10 tandem ASCT pts had maintenance. Response rates at 3 mos post-ASCT and best response rates after ASCT were similar between the maintenance and no maintenance groups (VGPR or better response rates were respectively 70% and 83% for the maintenance group and 75% and 85% for the no maintenance group) (Table 1). The median duration of maintenance was 11.1 mos (0.5-55.1) and 56% had stopped for progression.Overall median PFS was 41.3 mos (95%CI= 34.6-54.3) and overall median OS was 96.7 mos (95%CI lower bound= 64.9). For pts on lenalidomide maintenance, median PFS was 51.5 mos (95%CI= 35.9-61.8) and median OS was not reached on the study duration. Pts on maintenance had a significantly shorter median OS after relapse when compared to pts without maintenance (9.2 vs 19.9 mos, p= 0.006).Sixty-eight pts relapsed (50%), 40 in the maintenance group and 27 in the no maintenance group (Table 2). Overall, biochemical relapse was the most frequent type of relapse (56%) in all pts. However, pts receiving maintenance more often relapsed clinically and pts in the no maintenance group more often experienced biochemical relapses. Six of the 7 cases of FLC escape (86%) were in the maintenance group. Clinical relapsers usually had at least 1 component of the clinical presentation at relapse that was the same as at diagnosis (Dx). Overall, the most frequent types of clinical relapse involved bone lesions (51%), anemia (43%) and extramedullary disease (34%), the latter being more frequent in the maintenance group (40% vs 22%).Correlations between hypercalcemia at Dx and at relapse (positive correlation; coefficient= 0.45, p= 0.0064) and extramedullary disease at Dx and at relapse (positive correlation; coefficient= 0.39, p= 0.0201) were significant.By univariate analysis, maintenance (OR= 3.866, 95%CI= 1.333-11.211, p= 0.013) and high LDH at Dx (OR= 1.009, 95%CI= 1.001-1.016, p= 0.027) were associated with a clinical pattern of relapse. Bone lesions versus no bone lesions at progression were: 1) less likely to relapse early (OR= 0.178, 95%CI= 0.037-0.849, p= 0.030); 2) had a significantly longer median PFS (34.3 vs 15.6 mos, p= 0.0002); 3) had a longer OS (79.4 vs 36.3 mos, p= 0.031) and 4) had a longer OS after relapse (13.9 vs 3.7 mos, p= 0.003).ConclusionsThe most common pattern of first relapse was biochemical. Although we cannot exclude an effect of pt bias regarding use of maintenance, we observed an impact of maintenance on the pattern of relapse, with more clinical relapses. For pts relapsing on maintenance, cases of FLC escape and of extramedullary disease at relapse were also more frequent and OS after relapse tended to be shorter. High LDH at Dx was also associated with a clinical pattern of relapse. Interestingly, pts presenting with bone lesions at progression had better outcomes. [Display omitted] [Display omitted] DisclosuresCote:Takeda: Honoraria; Janssen: Honoraria. Reece:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Merck: Research Funding; Otsuka: Honoraria, Research Funding. Chen:Takeda: Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Prica:Celgene: Honoraria; Janssen: Honoraria. Tiedemann:Janssen: Honoraria; Celgene: Honoraria. Trudel:Amgen: Honoraria; Oncoethix: Research Funding; BMS: Honoraria; Glaxo Smith Kline: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Equity Ownership, Honoraria. Kukreti:Lundbeck: Honoraria; Celgene: Honoraria; Amgen: Honoraria.

Outcomes of Salvage Stem Cell Transplantation in Hodgkin Lymphoma in a Single Institution in the Modern Era

Background: Though overall Hodgkin lymphoma (HL) carries one of the best outcomes among lymphoma, about 40% of patients relapse and/or fail to respond to initial therapy. Out of those about half can be cured with salvage therapy followed by high dose therapy and autologous stem cell transplantation (ASCT) while eligible patients who fail and/or relapse after HDT-ASCT are offered nonmyeloablative stem cell transplantation. Achieving a negative PET response prior to ASCT correlate with superior outcome in HL regardless of their clinical presentation. More recently novel therapies have emerged in the field from brentuximab vedotin approved in r/r setting in HL as well as checkpoint inhibitors currently in trials with very promising results. This study analyzed a cohort of HL pts transplanted at our institution over the last 5 years to identify potential new patterns in the evolving landscape of HL.Methods: We performed a retrospective analysis of r/r HL pts referred to our center for salvage therapy at our institution between 2009 and 2014 using the Blood and Bone marrow transplant database at HUMC.Results: A total of 66 patients with r/r HL transplanted at HUMC were identified. Baseline characteristics were as follows: male 57%, female 43%, median age 36.8y (range 16-66), Frontline therapy was ABVD in all but one pt who received Gemzar, Vinorelbine, Doxil; and 27% pts received consolidation w/ radiation. Median time to relapse was 7mo (range 0.93-87mo), stage at first relapse I-0, II-33%, III-20%, IV-23%, NA 24%. The salvage regimen used was ICE in 54 pts, brentuximab vedotin in 8 pts and HCVAD in 4 pts. Involved field radiation was used in 10% at salvage prior to HDT-ASCT. Responses after first salvage were as follows: PET-CR 59%, CT-CR 5%, PR-14%, PD-12%, NA-10%. As per our practice, pts not in CR after first salvage continue to the next salvage until they reach a CR. Pts not in CR after 2 lines of salvage were considered for allogeneic stem transplantation (alloSCT). Conditioning regimen was BEAM prior to ASCT, reduced intensity (fludarabine-based) prior to alloSCT. Source of allo stem cells was: MRD in 7 pts, MUD in 3 pts, haploidentical donor in 2 pts. A total of 59 pts had ASCT, 6 pts had alloSCT as first transplant (primary refractory), while 6 pts underwent alloSCT for relapse after ASCT. Disease status post first transplant was as follows: PET-CR 76%, CT-CR 17%, PR-1%, PD-6%. All 6 alloSCT pts are alive in remission, while 13 out of 59 ASCT pts have relapsed, 7 relapses occurred within the first year, 3 within the second year post ASCT. Out of 6pts with alloSCT after ASCT relapse, 4 pts are alive in CR, one died from PD, one died from PTLD (in CR from HL). After a median follow up of 24.5 mo (3.7-70), the 3y PFS and OS are 73% and 95% respectively. For CR and PR after first salvage to SCT pts, median PFS and OS has not been reached. For SD/PD after first salvage therapy pts median PFS is 14.5mo, median OS 47mo. No significant difference in mPFS and mOS is seen in pts who received one vs more than one salvage therapy prior to ASCT or had radiation as part of frontline or salvage therapy.Conclusion: We report on a consecutive series of high-risk r/rHL. Our results demonstrate an improved outcome compared to historical data. Pts requiring more than one salvage prior to SCT while having mPFS of only 14.5 mo, have prolonged survival at median 47 mo.While the number is small, selected young pts with high risk relapsed HL may benefit from alloSCT. Strategy of requiring CR prior to SCT, and alloSCT (instead of ASCT) in pts requiring more than 2 consecutive salvage regimens, availability of novel agents, diminishing use of RT may have contributed to observed improved outcomes. DisclosuresFeldman:Pharmacyclics/JNJ: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau. Vesole:Idera Pharmaceuticals: Research Funding; Celgene Corporation: Speakers Bureau. Skarbnik:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau. Goy:Acerta: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/JNJ: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Clinical Outcomes and Prognostic Factors of Front-Line Autologous Stem Cell Transplantation in Patients with Extranodal NK/T-Cell Lymphoma

IntroductionExtranodal NK/T cell lymphoma (ENKTL) is a rare and aggressive lymphoma subtype, but standard front-line therapy has not been established. The clinical outcome of patients (pts) with ENKTL after the treatment of conventional chemotherapy, especially pts with advanced stage, was generally poor. Therefore, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) as a consolidation could be one of promising strategies to improve the outcome of ENKTL. However, there have been few studies reporting the survival outcome or prognostic significances of front-line ASCT in pts with ENKTL. Thus, the aim of this study was to investigate the outcome of pts with ENKTL who had undergone front-line ASCT.Patients and methodsWe consecutively enrolled pts with ENKTL who achieved CR or PR after primary chemotherapy ± radiotherapy and underwent front-line ASCT from 8 institutions from Jan 2005 to Dec 2013. Pts who were performed ASCT for salvage setting after relapse were excluded. Pts were classified as limited or advanced diseases according to Ann Arbor stage, and NK/T cell prognostic index (NKPI), which included the presence of B symptom, stage III or IV, elevated serum lactate dehydrogenase (LDH) level, and regional lymph node involvement, were determined for prognosis. Treatment response was assessed according to the International Working Group response criteria. The progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method.ResultsA total of 56 pts (39 male, 17 female) with median age of 47 years (range, 18-64) was included in this analysis. Twenty-seven pts (52%) were advanced disease and 18 (32%) had B symptoms at diagnosis. ECOG performance was ≥ 2 in 7 (13%) and serum LDH level was elevated in 25 (45%). Thus, 36 pts (64%) were classified as high risk (≥ 2 factors) by the NKPI. Pts with advanced disease were associated with worse performance status, higher risk of NKPI, and more frequent extra-upper aerodigestive (EUA) origin than those with limited disease.All pts received systemic chemotherapy including non-anthracycline-based (n=45, 80%) or CHOP/CHOP-like regimens (n=11, 20%). Involved field radiotherapy or chemoradiotherapy was given to 24 (83%) of pts with limited disease. The median time from diagnosis to ASCT was 6.7 months (range, 3.2-10.3), and pretransplant disease status consisted of 37 pts (66%) with complete response (CR) and 19 pts (34%) with partial response (PR). Only one treatment-related death (2%, fungal pneumonia) occurred following ASCT. With a median follow-up of 46.5 months (range, 3.7-109.5), 4-year PFS and OS were 50.5% (95% CI, 43.1-57.9) and 54.6% (95% CI, 46.6-62.6), respectively. Pts with advanced disease had inferior 4-year PFS (39.4% vs 63.2%, P=0.006) and OS (24.3% vs 69.9%, P=0.009), compared to pts with limited disease. CR achievement at transplantation was significantly associated with better PFS (4-year, 65.2% vs 21.1%, P=0.001) and OS (4-year, 67.1% vs 32.7%, P=0.006) than those with PR. This result was consistently important in pts with advanced disease (4-year PFS, 66.7% vs 8.3%, P=0.007). Multivariable analyses were performed separately in 2 steps. In the first step, analysis included all pts (N=56) and demonstrated that high risk of NKPI (HR, 3.10; 95% CI, 1.16-8.26), poor ECOG performance (HR, 3.84; 1.31-11.29), and PR at transplantation (HR, 4.22; 1.89-9.43) were independent predictors for worse PFS. In the second step, pts were stratified by stage. In the pts group with advanced stage (N=27), PR at transplantation (HR, 3.27; 1.07-10.04) and CHOP/CHOP-like primary chemotherapy (HR, 8.26; 1.59-43.05) were associated with higher risk of progression in multivariable analysis. In the pts group with limited stage (N=29), multivariable models revealed high risk of NKPI (HR, 4.22; 1.10-16.19) and EUA origin of anatomic subtype (HR, 10.02; 2.07-48.41) were independently associated with shortened PFS.ConclusionThis is the largest study that specifically focused on the outcomes of front-line ASCT in pts with ENKTL. Our study represents that non-anthracycline-based chemotherapy followed by ASCT would be feasible and active treatment option for ENKTL. NKPI and pretransplant CR achievement were important factors for predicting clinical outcomes, particularly NKPI in limited disease and pretransplant response in advanced disease. DisclosuresNo relevant conflicts of interest to declare.