Post-relapse Overall Survival Research Articles

Guideline-Based Follow-Up Outcomes in Patients With Gastrointestinal Stromal Tumor With Low Risk of Recurrence

Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure. To evaluate the outcomes of guideline-based follow-up in low-risk GIST. This multi-institutional retrospective cohort study involving Italian Sarcoma Group reference institutions evaluated patients with GIST who underwent surgery between January 2001 and June 2019. Median follow-up time was 69.2 months. Data analysis was performed from December 15, 2022, to March 20, 2023. Patients with GIST at low risk according to Armed Forces Institute of Pathology criteria were included provided adequate clinical information was available: primary site, size, mitotic index, surgical margins, and 2 or more years of follow-up. All patients underwent follow-up according to European Society for Medical Oncology (ESMO) guidelines. The primary outcome was the number of tests needed to identify a relapse according to ESMO guidelines follow-up plan. Secondary outcomes included relapse rate, relapse timing, disease-free survival (DFS), overall survival (OS), GIST-specific survival (GIST-SS), postrelapse OS, secondary tumor rates, and theoretical ionizing radiation exposure. An exploratory end point, new follow-up schedule proposal for patients with low-risk GIST according to the observed results, was also assessed. A total of 737 patients (377 men [51.2%]; median age at diagnosis, 63 [range, 18-86] years) with low-risk GIST were included. Estimated 5-year survival rates were 95.5% for DFS, 99.8% for GIST-SS, and 96.1% for OS. Estimated 10-year survival rates were 93.4% for DFS, 98.1% for GIST-SS, and 91.0% for OS. Forty-two patients (5.7%) experienced disease relapse during follow-up (9 local, 31 distant, 2 both), of which 9 were detected after 10 or more years. This translated into approximately 1 relapse detected for every 170 computed tomography scans performed, with a median radiation exposure of 80 (IQR, 32-112) mSv per patient. Nongastric primary tumor (hazard ratio [HR], 2.09; 95% CI, 1.14-3.83; P = .02), and KIT mutation (HR, 2.77; 95% CI, 1.05-7.27; P = .04) were associated with a higher risk of relapse. Second tumors affected 187 of 737 patients (25%), of which 56 were detected during follow-up and represented the primary cause of death in these patients. In this cohort study on patients affected by low-risk GISTs, the risk of relapse was low despite a follow-up across 10 or more years. These data suggest the need to revise follow-up schedules to reduce the anxiety, costs, and radiation exposure of currently recommended follow-up strategy.

Validation of POD24 As a Robust Early Clinical End Point of Poor Survival in Mantle Cell Lymphoma from 1280 Patients on Clinical Trials

Background The prognosis of mantle cell lymphoma (MCL) has largely improved in the past decade; however, the disease is characterized by a heterogeneous clinical course. Several retrospective studies identified early progression of disease (i.e. within two years, POD24) as a potential overall survival (OS) surrogate, but this has not been validated in cohorts of patients prospectively included in clinical trials in rituximab maintenance era. Methods We performed a pooled analysis of French patients with MCL included in six randomized clinical trials (EU-MCL younger NCT00209222, LyMA NCT00921414, LyMA101 NCT02896582, EU-MCL elderly NCT00209209, MCL-R2 NCT01865110 and RiBVD NCT01457144). Survival analysis using Landmark approach evaluated the association of POD24 status with post-event OS for all patients: starting from POD24 event or two years for patients without POD24 event. Logistic regression models were used to evaluate the association between POD24 status and (1) clinico-biological factors at diagnosis; (2) autologous stem cell transplantation at end-of-induction (ASCT) and anti-CD20 maintenance (RM) in responding patients after induction only. Results Among 1386 MCL patients, 106 censored for clinical follow-up before 24 months were excluded from the analysis, leading to 1280 patients evaluable for POD24 status: 299 with a POD24 event and 981 without. The 299 (23%) patients with a POD24 event had a post-event median OS of 9.3 months (95% CI 8.4-11.8) versus not reached in patients without POD24 event (95% CI 97.8-NR). Within the 981 non-POD24 patients, 314 presented a late relapse with a post-relapse median OS of 49.4 months (95% CI 30.4-56.8), significantly longer than OS of POD24 patients (HR=0.39; 95%CI 0.31-0.48; p<0.001). Compared to patients without a POD24 event, POD24 patients were older, had more frequently a performance status >1, elevated LDH and higher leucocytes leading to higher MIPI scores (high-risk MIPI 61% vs. 29%; p<0.001), more frequent blastoid variant (24% vs. 9%; p<0.001) and Ki67 > 30% (45% vs. 23%, p<0.001). Regarding treatment, POD24 patients had less frequently received high-dose cytarabine (21% vs. 39%, p<0.001) as well as ASCT (26% vs. 47%, p<0.001). In a final model, including baseline factors and treatment strategies, induction was not associated with risk of POD24, and only baseline variables (age, performance status, LDH, leucocytes and Ki67>30%) remained significantly associated with POD24 status. Within responding patients only (CR/CRu/PR at end-of-induction, n=1000), 150 had a POD24 event, and ASCT or RM were not significantly associated with POD24 status whereas age, LDH and Ki67>30% remained significant. Conclusion Using this large dataset of patients included in clinical trials, we confirm that POD24 can be used as a surrogate for OS in MCL. ASCT as well as RM have not a clear benefit to prevent early relapse within two years after the diagnosis in responding patients at end-of-induction.

Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%, P = 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%, P = 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11-0.68], P = 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18-0.98], P = 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42-7.05], P = 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted.

Similar Risk of Relapse and Survival with Post-Transplant Cyclophosphamide Compared to Standard Gvhd Prophylaxis after Allogeneic Hematopoietic Cell Transplantation for AML and MDS

Similar Risk of Relapse and Survival with Post-Transplant Cyclophosphamide Compared to Standard GVHD Prophylaxis after Allogeneic Hematopoietic Cell Transplantation for AML and MDS Background: Post-transplant cyclophosphamide (PTCy) is frequently used after allogeneic hematopoietic cell transplant (HCT) as it results in lower rates of graft versus host disease (GVHD). In addition to its predominant use in haploidentical and HLA mismatched donor HCT, PTCy showed potential to become the standard of care GVHD prophylaxis in a setting of HLA matched related and unrelated donor HCT as well (Bolaños-Meade, Lancet 2019). However, recent registry study reported higher risk of relapse after PTCy-based vs.calcineurin inhibitor (CNI) and methotrexate (MTX) GVHD prophylaxis in patients with acute myeloid leukemia (AML) receiving matched sibling donor HCT (Nagler, Transplant Cell Ther 2022). Thus, additional studies are needed to determine whether the benefit of GVHD prevention with PTCy comes at the cost of compromising the graft versus leukemia effect yielding higher relapse of AML and myelodysplastic syndromes (MDS) after HCT. In this retrospective study, we compared the HCT outcomes of PTCy-based vs. CNI-based GVHD prophylaxis in patients with AML and MDS. Methods: We included patients with AML and MDS who received an allogeneic HCT in first or second complete remission at our institution from 1/1/2014 to 12/31/2019. Patients received either a PTCy-based or a CNI-based GVHD prophylaxis regimen. CNI-based regimen consisted of either CNI/sirolimus +/- other (CNI/Siro group) or CNI/MTX +/- other (CNI/MTX group). The graft source in all the patients was peripheral blood (n=582) or bone marrow (n=23). Results: Total of 605 patients were identified: 442 with AML and 163 with MDS (Table 1.). GVHD prophylaxis with PTCy was used in 137 (23%), CNI/Siro in 402 (66%) and CNI/MTX in 66 (11%) patients. The PTCy group had higher proportion of patients who were Caucasian, received haploidentical donor HCT, reduced intensity (RIC) or non-myeloablative (NMA) conditioning or a bone marrow graft. Otherwise, baseline characteristics were similar between the GVHD prophylaxis groups. With a median follow up of 47 months, 149 (25%) patients relapsed, and 265 (44%) patients died. The probability of relapse at 2 years after HCT was similar between the GVHD prophylaxis groups: 23% in PTCy, 26% in CNI/Siro and 23% in CNI/MTX (p=0.94) (Figure 1). Similarly, there were no significant differences in 2-year overall survival (OS) between the groups: 58% in PTCy, 62% in CNI/Siro and 69% in CNI/MTX (p=0.33). We also observed no differences in non-relapsed mortality (NRM) between the groups. Median time to post-HCT relapse was 175 days in PTCy group, 180 days in CNI/Siro group and 131 days in CNI/MTX group. Management for post-HCT relapse included chemotherapy alone (n=58), chemotherapy +/- targeted therapy (n=53), chemotherapy + donor lymphocyte infusion (n=6), second HCT (n=3) and supportive care (n=29). GVHD prophylaxis groups did not differ by type of treatment used for relapse. Post-relapse OS at 2 years was 6% in PTCy, 20% in CNI/Siro and 31% in CNI/MTX groups (p=0.34). In multivariable analysis, the type of GVHD prophylaxis regimen did not significantly influence the post-HCT relapse, NRM, OS or post-relapse survival. Relapse was affected by DRI (p<0.001) and by type of conditioning regimen (p=0.002). NRM was influenced by HCT-CI (p=0.007) and by type of conditioning regimen (p=0.006). OS was inferior with high/very high risk DRI (p<0.001) and HCT-CI ≥ 3 (p<0.001). Survival after post-HCT relapse was better in patients relapsing >12 months after receiving HCT (p=0.003) and in those receiving treatment other than supportive care (p<0.001). Conclusion: In patients with AML and MDS receiving allogeneic HCT, we found similar risk of relapse and survival with PTCy-based and standard GVHD prophylaxis regimens. Survival after post-HCT relapse was also similar between the GVHD prophylaxis groups. The findings of this study support the use of PTCy-based regimen as GVHD prophylaxis after allogeneic HCT in patients with AML and MDS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Analysis of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Hematological Malignancies: A Single-center Study

To analyze the survival, prognostic factors, and prevention of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies, and explore the relationship between immune reconstruction, loss of human leukocyte antigen (HLA-loss) and relapse after transplantation. From July 2012 to June 2020, 47 patients with hematological malignancies who relapsed after allo-HSCT were retrospectively analyzed, including 20 cases undergoing matched-sibling donor transplantation (MSD), 26 cases undergoing haploidentical transplantation (HID), and 1 case undergoing matched-unrelated donor transplantation (MUD). Multivariate analysis was used to analyze the risk factors related to post-relapse overall survival (PROS). All the 47 patients were implanted successfully. The cumulative incidence of grade Ⅱ-Ⅳ, Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 40.4%, 10.6%, and 31.9%, respectively. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD in HID group was 42.3% and 11.5%, while in MD group was 38.1% and 9.5% (P=0.579, P=1.000), and the incidence of cGVHD in the two groups was 34.6% and 28.6% (P=0.659). The PROS of patients with NK cell absolute count > 190 cells/μl 30 days after transplantation was higher than that of patients with NK cell absolute count ≤190 cells/μl (P=0.021). The 1-year and 3-year PROS of all the patients was 68.1% and 28.4%, respectively, while in the HID group was 78.9% and 40.3%, in the MD group was 54.4% and 14% (P=0.048). Multivariate analysis showed that grade Ⅱ-Ⅳ aGVHD and time of relapse < 3 months were independent risk factors of PROS (P<0.05). The therapeutic effect of haploidentical transplantation in patients with relapsed hematological malignancies after allo-HSCT is better than that of matched donor transplantation. The high absolute count of NK cells 30 days after transplantation can increase PROS. Grade Ⅱ-Ⅳ aGVHD and time of relapse < 3 months have prognostic significance for long-term survival of patients with relapsed hematological malignancies after transplantation.

Clinical and biological features prognostic of survival after relapse of INRGSS-stage MS pattern neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.

10044 Background: Neuroblastoma (NB) presenting with INRGSS MS metastatic pattern highlights the extreme heterogeneity within NB and subsequent difficulty in risk assignment. Depending on tumor biology, patients with stage MS disease may be classified as very-low risk or as high-risk. While outcomes at initial diagnosis have been well-described, outcomes after relapse are less well defined. Methods: From the INRG Data Commons, we investigated clinical and biological characteristics of patients diagnosed 1984-2021 with stage MS pattern NB (INSS stage 4s, INSS stage 4 or INRG stage MS) who subsequently experienced disease relapse or progression, excluding patients whose first event was death. Using Kaplan-Meier methods, post-relapse overall survival (OS)± standard error (SE) was calculated from the time of first relapse/progression until death or last contact, overall and by era of diagnosis: &lt; 2000 vs ≥2001. Univariate Cox models were used to identify factors prognostic of post-relapse OS. Results: 209 patients met eligibility criteria,103 diagnosed &lt; 2001 and 106 ≥2001. Of patients diagnosed ≥2001, 89% (n = 94) were &lt; 365 days old at diagnosis; tumors were MYCN amplified in 21% (21/102) and diploid in 31% (20/64). Of this same cohort, time from initial diagnosis to relapse was &lt; 6 months in 40% (n = 42), 6-12 months in 25% (n = 26), and &gt; 12 months in 36% (n = 38) of patients. Of 60 patients with known site of relapse/progression diagnosed ≥2001, 73% (44) were metastatic (29) or primary plus metastatic (15). Among these, 16% (5/32) remained stage MS pattern while 84% (27/32) had metastatic sites beyond MS sites. Five-year post-relapse OS±SE was 53±3.5% overall (n = 209), and higher for those diagnosed ≥2001 (62±5.0%; n = 106) compared to those diagnosed &lt; 2001 (44±4.9%; n = 103) (p = 0.0046). In patients diagnosed ≥2001, factors prognostic of superior post-relapse OS included: age &lt; 365 days; not Hispanic; MYCN non-amplified; no 1p loss/aberration, hyperdiploidy; low/intermediate MKI; LDH &lt; 1400 U/L, favorable INPC histology; and &lt; 12 months from initial diagnosis to first relapse. Conclusions: Most patients with relapsed stage MS NB have metastatic relapse and these relapses more commonly occur at sites outside liver, skin, and bone marrow. Patients diagnosed ≥2001 with MS pattern NB have substantially better post-relapse OS compared to those diagnosed &lt; 2001. In the cohort of patients with MS pattern NB diagnosed ≥2001, most of the well-accepted prognostic factors for OS at diagnosis are also prognostic of post-relapse OS.

Patterns of relapse after immunotherapy in patients with high-risk neuroblastoma.

10043 Background: While the addition of anti-GD2 immunotherapy led to improvement in outcomes in patients on the Children’s Oncology Group (COG) ANBL0032 study, relapse remains a concern. Prior studies demonstrated the prognostic importance of time to first relapse, however, the effect of immunotherapy on timing and patterns of relapse in neuroblastoma (NBL) have yet to be evaluated. The purpose of this exploratory analysis was to describe the impact of immunotherapy on patterns of relapse in patients with high-risk NBL, including a descriptive comparison of sites of relapse based on post-consolidation treatment received [dinutuximab with cytokines and isotretinoin (DIN) vs isotretinoin alone (ISO)]. Methods: A retrospective, descriptive analysis of patients on ANBL0032 was performed, including patients randomized to DIN or ISO and those non-randomly assigned to DIN after ISO arm closure. Pt characteristics including age, stage, MYCN amplification status, tumor grade, mitosis-karyorrhexis index (MKI) and ploidy were summarized descriptively and relapse sites were tabulated. For DIN patients who subsequently relapsed, overall survival (OS) was calculated starting from the time of first relapse after enrollment on ANBL0032 (“post-relapse OS”). Kaplan-Meier OS curves were generated based on site of relapse. Results: The analytic cohort included 1,431 (DIN = 1,327; ISO = 104) patients. Among DIN patients, 492 relapsed, many in &gt; 1 site. In the randomized cohort (n = 248), 122 relapsed (DIN = 68/144; ISO = 54/104). The frequencies (DIN; ISO) by site of relapse in the randomized cohort were: bone (53%; 54%), CNS (16%; 11%), lymph node (13%; 17%), abdominal (10%; 17%), paraspinal (6%; 2%), liver (3%; 4%), other soft tissue (22%; 7%). A higher proportion of ISO patients had marrow relapse (29.4% DIN; 48.2% ISO); however, the proportion of DIN patients with lung relapses appeared higher (9% vs 2%). Among all relapsed patients, the proportion with bone relapse did not appear to differ between treatment groups, regardless of MYCN status. Among patients with MYCN amplified disease, the proportion with marrow relapse did not appear to differ based on treatment [21/149 (14.1%) DIN; 3/20 (15.0%) ISO]; however, among patients with MYCN non-amplified disease, the proportion with marrow relapse appeared higher in the ISO group [16/23; 69.6%] vs the DIN group [52/193 (26.9%)]. Conclusions: In this exploratory analysis of patients on COG ANBL0032, the pattern for site of relapse appears to differ between patients treated with DIN vs ISO. While immunotherapy remains the treatment of choice in this population, the findings from this retrospective exploratory analysis warrant further investigation to decrease the risk for post-immunotherapy relapse. Clinical trial information: NCT00026312.

Outcomes of Autologous Hematopoietic Cell Transplantation in Older Patients with Diffuse Large B-Cell Lymphoma

Data for outcomes after autologous hematopoietic cell transplantation (auto-HCT) in diffuse large B-cell lymphoma (DLBCL) patients ≥70 years are limited. Auto-HCT is feasible in older DLBCL patients. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes of auto-HCT in DLBCL patients aged 60 to 69 years (n = 363) versus ≥70 years (n = 103) between 2008 and 2019. Non-relapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. All patients received BEAM conditioning (carmustine, etoposide, cytosine arabinoside and melphalan). On univariate analysis, in the 60 to 69 years versus ≥70 years cohorts, 100-day NRM was 3% versus 4%, 5-year REL was 47% versus 45%, 5-year PFS 40% versus 38% and 5-year OS 55% versus 41%, respectively. On multivariate analysis, patients ≥70 had no significant difference in NRM (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.85-2.39), REL (HR 1.11, 95% CI 0.79-1.56), PFS (HR 1.23, 95% CI 0.92-1.63) compared to patients 60 to 69 years. Patients ≥70 years had a higher mortality (HR 1.39, 95% CI 1.05-1.85, p=0.02), likely because of inferior post-relapse OS in this cohort (HR 1.82, 95% CI 1.27-2.61, P = .001). DLBCL was the major cause of death in both cohorts (62% versus 59%). Older patients should not be denied auto-HCT solely on the basis of chronological age.

Adult-type non-rhabdomyosarcoma soft tissue sarcomas in pediatric age: Salvage rates and prognostic factors after relapse

PurposeThough the prognosis for patients with pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is generally good, the chances of being cured after relapse are limited. This report describes a series of relapsing NRSTS patients treated at a referral center for pediatric sarcoma, investigating the pattern of relapse, salvage rates, and factors correlating with the final outcome. MethodsThe analysis concerned 103 patients <21 years old with relapsing adult-type NRSTS treated from 1985 to 2020. For risk-adapted stratification purposes, the patient outcome was examined using univariable and multivariable analyses based on patients’ clinical features at first diagnosis, first-line treatments, clinical findings at first relapse, and second-line treatments. ResultsThe first relapse occurred within 2–102 months (median 14 months) after patients' first diagnosis and was local in 47%, metastatic in 34%, and both in 19%. Treatment at relapse included chemotherapy in 72 patients, radiotherapy in 38, and surgery in 55. The median overall survival (OS) was 20 months. Post-relapse OS was 56.1%, 25.8%, and 19.1% at 1, 5, and 10 years, respectively. Cox's multivariable regression analysis showed that OS was significantly better for patients with local and late relapses (occurring more than 12 months after their first diagnosis) and for those achieving secondary remission. ConclusionThe outcome of patients with recurrent NRSTS is poor. The above-mentioned variables (type and time of relapse and achievement of secondary remission) were combined in a risk-adapted model to develop a tool for estimating the chance of salvage and deciding the best second-line treatment approach.

Post-relapse survival in Waldenstrom macroglobulinemia patients experiencing therapy failure following autologous transplantation.

Waldenström macroglobulinemia (WM) is a rare B-cell lymphoproliferative malignancy. Autologous hematopoietic cell transplantation (auto-HCT) is considered in a subset of WM patients with relapsed disease. While registry data has shown a benefit for auto-HCT in relapsed WM, there is a paucity of data on outcomes of patients relapsing after auto-HCT. Eligibility criteria included adult patients with relapsed/refractory WM who underwent auto-HCT between 2007 and 2017. The primary endpoint was post-relapse overall survival (PR-OS). Secondary endpoints were to identify factors prognostic of PR-OS. Of the 48 patients with WM who underwent auto-HCT, 22 (46%) experienced relapse following auto-HCT. Median PR-OS of relapsed WM patients after auto-HCT (n=22) was not reached (NR) (95% confidence interval [CI]: 17.5months-NR). Among patients who relapsed <1year versus ≥1year from auto-HCT, the median PR-OS was 18.4months (95%CI: 0.8-NR) months and NR (95%CI: 17.5-NR), respectively (p=0.06). Of note, disease status at the time of transplant, CR/VGPR versus partial remission did not appear to impact PR-OS. The median PR-OS was significantly longer in patients who received ibrutinib in the post-transplant setting compared to those who did not (NR vs. 18.4 months, 95%CI: 9.1-NR, p=0.02). On univariable analysis, the presence of complex karyotype (RR=4.87, 95% CI=1.22-19.53) and a higher number of prior lines of therapy (RR=1.81, 95% CI=1.23-2.67) were associated with a significantly higher risk of relapse. This is the only study to date that evaluated outcomes of WM patients who relapsed following auto-HCT and provides a benchmark for future trials evaluating survival following auto-HCT relapse.

Impact of Novel Agents on the Outcomes of Patients with Classic Hodgkin Lymphoma That Relapsed after Autologous Stem Cell Transplant

Impact of Novel Agents on the Outcomes of Patients with Classic Hodgkin Lymphoma That Relapsed after Autologous Stem Cell Transplant

Long-Term Outcomes of Patients with Peripheral T-Cell Lymphoma after Autologous Hematopoietic Cell Transplantation

Introduction: Patients with T-cell lymphoma have variable clinical manifestations and outcomes depending on the histology and their response to therapies. However, the overall outcomes are not as good as their B-cell lymphoma counterpart with induction chemotherapy alone. Therefore, autologous transplant is often used as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We have reported previously on Stanford experience of these patients who underwent autologous transplant before 2007 (BBMT 2008, 14:741). Here, we reported a retrospective review of patients in the modern era (2008-2018) with emphasis on the impact of pre-transplant disease status on outcomes and post-transplant relapse management. Method: Between July 1, 2008 and July 31, 2018, 102 consecutive patients with T-cell lymphoma received high dose chemotherapy/autologous hematopoietic cell rescue at Stanford and constitute the study cohort (Figure 1). This study cohort was selected for adequate follow-up (&amp;gt;2 years) after transplant. Progression free survival (PFS) and overall survival (OS) was estimated from the date of transplant using the Kaplan-Meier method. PFS and OS were compared between groups with different pre-transplant disease status based on response to the last pre-transplant therapies (CR1 vs. PR1 vs. CR2). Result: This study cohort included patients with peripheral T-cell lymphoma, non-specified (n=21), angioimmunoblastic T-cell lymphoma (n=50), ALK-negative anaplastic large-cell lymphoma (n=14), ALK-positive anaplastic large-cell lymphoma (n=5), extranodal NK/T cell lymphoma (n=9), enteropathy-type T-cell lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1) and hepatosplenic T-cell lymphoma (n=1). It had a male/female ratio of 61/41, and a median age of 58 years (range 23-71). At diagnosis the majority of the patients had stage III/IV disease (70%) and B symptoms (56%). The median time from diagnosis to transplant was 8.1 months (range 4-176). The majority of patients were in first complete remission (CR1, n=79) at the time of transplant, while others were in PR1 (n=11) or in CR2 (n=12) from last pre-transplant therapies. Ninety-one (89%) patients received high dose cyclophosphamide/carmustine/etoposide(CBV) and 11 patients received high dose carmustine/etoposide/cytarabine/melphalan (BEAM) prior to autograft infusion. Median follow-up post-transplant was 36.8 months (range 0.7-130) for the entire cohort. The estimated 3-year PFS and OS were 60% (95% CI 49-68%) and 75% (95% CI 65-82%), respectively (Figure 2A). Patients who were in CR1 had significantly better median PFS compared to patients in PR1 or CR2 (7.04 vs 1.19 years, p=0.039; 7.04 vs 0.48 years p=0.004, Figure 2B). The estimated 3-year PFS were 67% (95% CI 55-76%), 36% (95% CI 11-63%), and 29% (95% CI 8-56%) for the CR1, PR1 and CR2 groups respectively. Patients who were in CR1 also had significantly better median OS compared to patients in PR1 or CR2 (not reached vs 2.30 years, p=0.018; not reached vs 3.76 years p=0.045, Figure 2C).The estimated 3-year OS were 82% (95% CI 71-89%), 44% (95% CI 14-70%), and 53% (95% CI 21-78%) for the CR1, PR1 and CR2 groups respectively. In this cohort, there were no significant differences in either PFS or OS between different histology. Forty patients experienced disease relapse after transplant. The majority (n=28, 70%) of these patients received additional therapies including chemotherapy (n=13), brentuximab vedotin (n=12), HDAC inhibitor (n=7), and radiation (n=3) with a median systemic therapy of 2 (range 1-5). Thirteen patients eventually underwent allogeneic hematopoietic cell transplantation. The median OS after post-transplant relapse was 21.3 months (Figure 3). Both brentuximab vedotin and allogeneic transplant seemed to provide prolonged survival for these relapsed patients, with estimated 2-year post-relapse OS were 75% (95% CI 13-96%) and 63% (95% CI 28-84%) for the two groups respectively. Conclusion: Autologous transplant remains to be a good option as consolidation for patients with T-cell lymphoma, mostly in patients with first complete remission. While close to 40% of the patients experienced relapse after autologous transplant, additional therapies such as brentuximab vedotin or/and allogeneic transplant can provide long-term benefit for these patients. Disclosures Shizuru: Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Muffly:Servier: Research Funding; Amgen: Consultancy; Adaptive: Research Funding. Sidana:Janssen: Consultancy. Meyer:Orca Bio: Research Funding. Rezvani:Pharmacyclics: Research Funding. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents &amp; Royalties, Research Funding; Allogene Therapeutics Inc.: Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding. Negrin:Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; Biosource: Current equity holder in private company; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy.

Prognostic Factors for Postrelapse Survival after ex Vivo CD34+-Selected (T Cell-Depleted) Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma.

Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT. The median patient age was 56 years, and 82% had high-risk cytogenetics. Patients received a median of 4 lines of therapy pre-HCT, and 88% achieved at least a partial response (PR) before alloHCT. Of the 38% who received preemptive post-HCT therapy, 13 received donor lymphocyte infusions (DLIs) and 10 received other interventions. Relapse was defined as very early (<6 months; 28%), early (6 to 24 months; 50%), or late (>24 months; 22%). At relapse, 27% presented with extramedullary disease (EMD). The median postrelapse overall survival (OS) by time to relapse was 4 months for the very early relapse group, 17 months for the early relapse group, and 72 months for the late relapse group (P=.002). Older age, relapse with EMD, <PR before alloHCT, <PR by day +100, and no maintenance were prognostic for inferior postrelapse OS on univariate analysis. On multivariate analysis adjusted for age and sex, very early relapse (hazard ratio [HR], 4.37; 95% confidence interval [CI], 1.42 to 13.5), relapse with EMD (HR, 5.20; 95% CI, 2.10 to 12.9), and DLI for relapse prevention (HR, .11; 95% CI, 2.10 to 12.9) were significant predictors for postrelapse survival. Despite their shared inherent high-risk status, patients with MM have significantly disparate post-HCT relapse courses, with some demonstrating long-term survival despite relapse.

Outcomes for Double Hit Lymphoma Patients Identified Via Routine Vs Selective Testing for MYC Rearrangement

Outcomes for Double Hit Lymphoma Patients Identified Via Routine Vs Selective Testing for MYC Rearrangement

Postrelapse survival in diffuse large B-cell lymphoma after therapy failure following autologous transplantation

AbstractOutcomes for diffuse large B-cell lymphoma (DLBCL) patients relapsing after autologous hematopoietic cell transplantation (auto-HCT) have been historically poor. We studied outcomes of such patients using data from 4 transplantation centers. Eligibility criteria included adult patients (age ≥18 years) with DLBCL experiencing disease relapse after auto-HCT performed during 2006 to 2015. The time period was stratified into 2 eras (era 1, 2006-2010; era 2, 2011-2015). The primary end point was postrelapse overall survival (PR-OS). Secondary end points were factors prognostic of PR-OS. Of the 700 patients with DLBCL who underwent auto-HCT, 248 (35%) relapsed after auto-HCT. Median PR-OS of all relapsed DLBCL patients after auto-HCT (n = 228) was 9.8 months (95% confidence interval [CI], 7-15). Median PR-OS was significantly better for patients in complete (17.8 months; 95% CI, 7.9-41.6) vs partial remission at auto-HCT (7.1 months; 95% CI, 5.4-11; P = .01), those undergoing auto-HCT >1 year (12.8 months; 95% CI, 7.6-24.9) vs ≤1 year after DLBCL diagnosis (6.3 months; 95% CI, 4.5-9.2; P = .01), and those with late (56.4 months; 95% CI, 23.7-∞) vs early relapse (5.9 months; 95% CI, 4.5-8.8; P < .0001). On multivariate analysis, although late relapse (hazard ratio [HR], 0.21; 95% CI, 0.13-0.34; P < .0001) was associated with significantly lower mortality, the risk of mortality increased with age (HR, 1.25 per decade; 95% CI, 1.06-1.48; P = .009). This is the largest study to date to evaluate outcomes of DLBCL patients relapsing after auto-HCT. Our study provides benchmarking for future trials of chimeric antigen receptor T cells and other promising agents evaluating PR-OS after auto-HCT.

Retroperitoneal soft tissue sarcoma (RPS): Recent outcome improvement and refinement of treatment strategies at a single institution.

11041 Background: Extended surgery in retroperitoneal sarcoma (RPS) has resulted in less recurrences and better survival. We investigated whether outcome further improved, after the recent understanding of behavior of different RPS subtypes and introduction of multimodal therapies. Methods: Consecutive primary RPS operated at a single center were analyzed comparing 3 periods (2002-2006; 2007-2011; 2012-2016). Primary endpoints were overall survival (OS), crude cumulative incidence (CCI) of local recurrence and distant metastasis (LR, DM) for each subgroup: well differentiated (WDLPS), dedifferentiated G2 (G2DDLPS), G3 (G3DDLPS) liposarcoma, and leiomyosarcoma (LMS). Secondary endpoints: morbidity and post-relapse OS. Fisher/Chi-squared and Cochran–Armitage trends test were used. Survival was analysed by Kaplan-Meier/Cox PH or CCI/Fine Gray models in the competitive risk framework and compared with log-rank/Wald Gray tests. Multivariable analyses were performed. Results: Overall 437 RPS were operated: 82, 128 and 227 in the 1st, 2nd and 3rd period. Median follow-up was 125, 86 and 39 months. Complete resection (R0/R1) improved from 93.9% to 98.2% (p=0.059), median number of resected organs increased from 2 to 4 (p&lt;.0001). Postoperative morbidity did not change (18.3%, 16.4%, 22.5%; p=0.269). Administration of radiotherapy and chemotherapy (CT) differed over time according to different subtypes. 5-yr OS improved (63.2% to 74.7%, p=0.005), along with a non-significant reduction in LR CCI (18.2% to 16.4%, p=0.379) and no change in DM CCI. At multivariable analysis, study period remained an independent prognostic factor for OS among the other known risk factors (3rd vs 1st period HR: 0.33, p&lt;0.001). Subgroup analysis showed the following associations with better prognosis: 1. Improvement in 5-yr OS (from 55.0% to 70.7%, p=0.024) and LR (from 45.0% to 19.8%, p=0.060) in G2DDLPS, associated with more organs resected 2. Improvement in 5-yr OS (from 18.2% to 49.7%, p=0.035) and DM (from 70.0% to 19.8%; p=0.015) in G3DDLPS, associated with more anthracycline-based CT 3. A better 2-yr post-relapse OS (from 46.3% to 65.2%, p=0.122). Conclusions: OS of patients with DDLPS improved over time: in G2 this was associated with a refinement in the surgical approach, while in G3 with a more liberal use of anthracycline-based CT. New available therapies for recurring RPS may also have extended post-relapse OS. Prospective studies on perioperative CT for high risk RPS subtypes are eagerly awaited.

The impact of method of recurrence detection on esophageal/gastroesophageal junction (EGJ) cancer outcomes.

e15580 Background: Trimodality treatment (tx) with neoadjuvant chemoradiation (CRT) followed by esophagectomy is standard tx for locally advanced EGJ cancer. Post-operatively, there is no strong consensus about role of routine surveillance imaging. At the University of Rochester, patients (pts) have surveillance CT scans every 4-6 months (mos) for the first 2 years post-esophagectomy and every 6-12 mos for the next 3 years. Methods: Pts were identified who underwent esophagectomy for T1-T3 EGJ cancer between January 2011 and December 2015 at our institution. Objectives were to describe the impact of timing and methods of recurrence detection (MoRD) on patient outcomes. Recurrence-free (RFS) and overall survival (OS) were graphed via the Kaplan-Meier method. Results: 138 pts underwent esophagectomy for EGJ cancer: 107 (77.5%) were male, median age was 64, and 116 patients (84.1%) had adenocarcinoma. 112 pts (81.2%) had neoadjuvant CRT. The entire cohort’s median OS was 38.4 mos. 68 pts (49.3%) relapsed with a median RFS of 20.0 mos. Recurrence was detected by routine imaging in 36 pts (52.9%), imaging triggered by symptoms in 27 pts (39.7%), and symptoms alone in 5 pts (7.4%). Post-relapse median OS was 2.3 mos when detected based on symptoms alone, 5.0 mos when detected by imaging triggered by symptoms, and 13.7 mos when detected by routine scans (log-rank p = 0.041). There was no significant association between baseline patient/tumor characteristics or pathologic response and MoRD . 53 patients (77.9%) received salvage/palliative tx with a median of 2 tx (IQR = 1). There was no significant association between MoRD and number of salvage/palliative tx. Conclusions: 49.3% of pts relapsed after esophagectomy for EGJ cancer, consistent with current literature. Almost half of relapses were detected based on symptoms despite routine imaging. Increased OS for pts with relapse detected by routine scans is likely related to lead time bias, but may also be related to increased tx intensity or less aggressive tumors. MoRD did not have a measurable impact on number of lines of post-relapse tx. Prospective randomized trials are needed to determine real benefit of regular surveillance scans among EGJ cancer survivors.

Prognostic factors for survival after relapsed acute lymphoblastic leukemia (ALL): A Children’s Oncology Group (COG) study.

10008 Background: Survival of pediatric ALL patients (pts) now approaches 90%, but is historically poor for those who relapse. Methods: In the largest cohort assembled to date we analyzed overall survival (OS) rate post relapse, defined as duration between date of relapse and death, among pts diagnosed from 1996-2014 treated on 10 contemporary COG frontline trials. Comparisons of post-relapse OS were based on logrank tests, with two-sided p values reported. Results: Of 15,874 pts enrolled on frontline trials, 1,967(12%) relapsed. Relapse rates ranged from 35% in infant ALL to 9.7% in pts with NCI standard risk B-ALL. Rates were similar for T and B-ALL, 11% vs. 12%. Relapse patterns differed by phenotype: almost half of non-infant B-ALL relapses occurred late (≥36 mos), and at all time periods bone marrow (BM) relapse predominated. Conversely 65% of T-ALL relapses were early ( &lt; 18 mos) with similar number of isolated CNS (iCNS) and isolated BM (iBM) relapses. Median time to relapse was shorter for infant ALL and T-ALL (both 13.8 mos) compared to B-ALL (34.4 mos). The 5yr OS rates (±SE) after relapse for B, T, and infant ALL were 52±1%, 33±3% and 19±4%, respectively, with greater variability in OS by site in T vs. B-ALL. 5yr OS rates for pts with early BM relapse was similar for both B and T-ALL (28%), but pts with B-ALL who relapsed between 18-36 mos fared better than pts with T-ALL (OS 50±2% vs 34±8%, p = 0.014). The 5yr OS rates for pts with late relapses were 65±2% for B-ALL and 50±12% for T-ALL. In multivariable analysis, time to relapse, site of relapse, age &lt; 1 or &gt; 10 yrs at diagnosis, initial WBC &gt; 100K, and T-cell phenotype were associated with worse outcomes post relapse (all p &lt; 0.01). Sex, CNS status at diagnosis, or prior therapy on POG versus CCG/COG backbone did not influence OS. Compared to pts treated from 1988-2002 (Nguyen et al. Leukemia 2008), 5yr OS rate post relapse has improved over time for B-ALL from 37±2% to 52±1% (p &lt; 0.001) and T-ALL from 23±4% to 33±3% (p &lt; 0.05). 5-yr OS rates improved significantly for pts with iBM from 24±2% to 45±2% (p &lt; 0.001) and marginally for pts with iCNS from 59±3% to 65±3% (p = 0.15). Conclusions: In the modern era there are fewer relapses for B and T-ALL, however sites of recurrence and outcomes differ by phenotype. Infants continue to do poorly. Compared to prior analyses, survival after relapse is significantly improved.

Post-Relapse Survival in Diffuse Large B-Cell Lymphoma (DLBCL) Patients after Experiencing Therapy Failure Following Autologous Hematopoietic Cell Transplantation (auto-HCT)

Introduction The outcomes for DLBCL patients who relapse following auto-HCT have been historically poor. Using data from four transplant centers, we studied the outcomes of DLBCL patients who relapsed following auto-HCT and evaluated whether survival improved in the most recent time period with the advent of novel agents. Methods Eligibility criteria included adult (≥18 years) patients with DLBCL experiencing disease relapse following auto-HCT performed during 2006-2015. The time-period was stratified into two eras (era-1: 2006-2010 and era-2: 2011-2015). The primary endpoint was to determine post-relapse overall survival (PR-OS). Secondary endpoints included a comparison of PR-OS based on the timing of relapse post auto-HCT (early [≤1 year] vs late [>1 year]) and era of transplant (era-1 vs era-2). PR-OS was measured from the date of relapse following auto-HCT to date of death or last follow-up. Results Of the total 700 patients with DLBCL undergoing auto-HCT, 250 patients (36%) (n=113 from era-1 and n=137 from era-2) relapsed following auto-HCT between 2006 and 2015. Patient characteristics are shown in Table with a breakdown between the two eras. The median age was 59 years with male predominance. 92% were chemosensitive (n=230) at the time of auto-HCT. The median time to relapse post auto-HCT was 5.6 months (range: 0.8–96.6 months). Median lines of therapy for post auto-HCT relapse were 1 (range: 0-9), with the most common treatments being allogeneic HCT (21%), lenalidomide (18%) and on clinical trials (17%). Median follow-up of survivors post auto-HCT relapse was 39 months (range: 1-116 months). At 5-year post auto-HCT relapse, the PR-OS for the entire population was 25%, with a median PR-OS of 8.5 months (95% CI=6.3-11.5). Median PR-OS (in months) was significantly better for patients who had late relapse vs early relapse (56.4 [95% CI=23.7-∞] vs 5.5 [95% CI=4.1-7.2], respectively, p Conclusion In DLBCL patients who relapse following auto-HCT, there has been no significant improvement in PR-OS despite the advent of novel agents in the most recent era. More importantly, the outcomes are dismal for patients who relapse within 1 year of auto-HCT representing an urgent unmet need.

Revised International Staging System Is Predictive and Prognostic for Early Relapse (

The revised International Staging System (R-ISS) combines ISS with genetic markers and lactate dehydrogenase and can prognosticate newly diagnosed multiple myeloma (MM). Early relapse (<24 months) after upfront autologous hematopoietic cell transplantation (AHCT) strongly predicts inferior overall survival (OS). We examined the ability of R-ISS in predicting early relapse and its independent prognostic effect on postrelapse survival after an early relapse. Using the Center for International Blood and Marrow Transplant Research database we identified MM patients receiving first AHCT within 18 months after diagnosis with available R-ISS stage at diagnosis (n = 628). Relative risks of relapse/progression, progression-free survival (PFS), and OS were calculated with the R-ISS group as a predictor in multivariate analysis. Among early relapsers, postrelapse survival was tested to identify factors affecting postrelapse OS. The cumulative incidence of early relapse was 23%, 39%, and 50% for R-ISS I, R-ISS II, and R-ISS III, respectively (P < .001). Shorter PFS and OS were seen with higher stage R-ISS. R-ISS was independently predictive for inferior postrelapse OS among early relapsers, as was the presence of ≥3 comorbidities and the use of ≥2 induction chemotherapy lines. R-ISS stage at diagnosis predicts early post-AHCT relapse and independently affects postrelapse survival among early relapsers.