Upfront Autologous Stem Cell Transplantation Research Articles

Interim Results of a Risk-Adaptive Phase II Study: Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab (KRD-Dara) in Newly Diagnosed Multiple Myeloma (NDMM) at the Levine Cancer Institute (LCI)

Background: The combination of carfilzomib, lenalidomide and dexamethasone (KRd) has previously demonstrated deep and durable responses in patients with NDMM. A quadruplet regimen incorporating daratumumab (KRd-Dara) may further improve results. We report an interim analysis from stage 1 (Simon's optimal 2-stage design) of an ongoing minimal residual disease (MRD)-driven, single center phase 2 trial of KRd-Dara. Methods: The study design has been previously published (Bhutani et al, Blood 2020 Abstr 1388). Briefly, patients with NDMM (both transplant eligible and ineligible) were allowed one cycle of non-protocol therapy (if deemed necessary) and then 7 or 8 cycles of induction therapy with KRd-Dara (total induction cycles: 8). MRD assessment was performed by both next generation sequencing (NGS) and next generation flow cytometry (NGF) at the end of 8 cycles of induction, post- autologous stem cell transplantation (ASCT), and every 4 cycles of consolidation (maximum of 12 cycles). Post-induction treatment was dictated by an MRD-driven algorithm, using MRD (NGS, 10-5) to assign patients to one of the 3 study groups. The primary endpoint is complete response (CR) + stringent CR (sCR) at the completion of KRd-Dara induction therapy. Group A (MRD negative post-induction) proceeded directly to lenalidomide maintenance therapy deferring ASCT, if transplant eligible. Group B (MRD positive, transplant eligible) received upfront ASCT, KRd consolidation (maximum 12 cycles), and then lenalidomide maintenance. Group C (MRD positive after 8 cycles of induction, transplant ineligible) received KRd consolidation (maximum 12 cycles) followed by lenalidomide maintenance. Conversion to MRD negative status at any protocol specified time point allowed the patients to proceed to lenalidomide maintenance. Results: Stage 1 futility analysis criteria were met in November 2021 and stage 2 enrollment is actively ongoing. As of a data cutoff of 4/8/22, 30/39 patients have been enrolled. Twenty-three patients were enrolled in Stage 1. The median age of stage I patients was 60 (range 34- 76) years, 74% were male and 35% were Black. R-ISS stage 3 was present in 2 (8.7%), high-risk cytogenetics in 1 (4.4%) and gain 1q21 in 7 (30.4%). Fifteen patients (65.2%) received one cycle of pre-study treatment. All patients completed 8 total cycles of induction therapy. At the end of induction, CR + sCR was achieved in 15/23 (65.2%) patients with sCR in 52.2%, and very good partial response (VGPR) in 7 (30.4%). The MRD negativity rate was 69.6% (NGS, 10-5) and 43.5% (NGS, 10-6). The MRD negativity rate by NGF was 82.6% at 10-5and 47.4% at 10-6 sensitivity level in 23 and 19 evaluable patients, respectively; 43% of bone marrow specimen tested by NGF were hemodiluted. Concordance of MRD by NGS/ NGF at 10-5 was 16/23 (69.6% in agreement and 30.4% disagreement, Cohen's kappa: 0.183). Concordance of MRD by NGS/ NGF at 10-6 was 12/19 (63.2% in agreement and 36.8% disagreement, Cohen's kappa: 0.257). Grade 3-4 treatment related adverse events (>10% of patients) included hypophosphatemia (30%), hypertension (13%), and neutropenia (13%). Covid infection occurred in 7 (30.4%) patients; only one needed hospitalization. Other Infections (any grade) were seen in 15 (65.2%) patients. At least one dose reduction of carfilzomib was required in 5 (21.7%) patients, dexamethasone in 3 patients, and lenalidomide in 4 patients. Systemic injection reactions to subcutaneous daratumumab occurred in 5 (21.7%). Thromboembolic events happened in 3 patients. No patient discontinued treatment because of toxicity. There was no treatment-related mortality during stage 1. Post-induction, 16 patients (MRD negative) transitioned to lenalidomide maintenance, 5 patients (MRD positive) underwent ASCT, and 2 patients (MRD positive) proceeded to consolidation phase. Stem cell collection for eligible patients (n=22) was performed upon completion of induction; 5 patients failed to collect optimal target (3 million CD34+ cells/kg) during their first mobilization attempt. Survival results will be updated after stage 2 enrollment is completed, but as of data cutoff, no subjects in the Stage 1 cohort have progressed. Conclusions: The quadruplet regimen KRd-Dara as induction in NDMM leads to deep responses reflected in high rates of sCR and MRD negativity with an acceptable and well-tolerated safety profile. The stage 2 enrollment is ongoing.

MM-252 A Retrospective Review of Relapsed Multiple Myeloma Post Autologous Stem Cell Transplant: Data From an Indian Tertiary Cancer Center

Multiple myeloma (MM) relapsing post autologous stem cell transplant (ASCT) continues to have overall poor outcomes in low- to middle-income countries (LMICs), and the efficacy data on available salvage regimens is limited. Here, we report the treatment outcomes of such patients treated at an Indian tertiary cancer center. The primary objective was to determine the PFS with salvage treatment. Secondary objectives included objective response rates (ORR) and ≥ partial response (PR). Single-center retrospective study of MM patients relapsing post ASCT between January 2015 and October 2020, treated with salvage regimen and followed until January 2022. North Indian tertiary cancer referral center. Records of 51 relapsed MM patients were screened for the study. All of them received up-front ASCT followed by maintenance treatment and later relapsed. Six (8.5%) patients with incomplete treatment details were excluded. Forty-six patients were included in the study. PFS. Median age was 51 years (range 45-68 years); 67.8% were men. Thirteen (28.2%) patients had high-risk cytogenetics. An extramedullary pattern of relapse was seen in 7 (15.2%) patients. Pomalidomide-based salvage therapy (VPd, PCd) was used in 18 (39.2%) patients and VRd in 14 (30.5%) patients. ORR was 47.8% (24/46). CR was observed in 28.3% (13/46) of patients. After a median follow-up of 8.1 months (IQR 3.1-26.7 months), 30 patients progressed and the median PFS was 6.75 months (95% CI 0.7-27.5 months). Median PFS did not differ by type of salvage treatment, such as pomalidomide versus non-pomalidomide (hazard ratio [HR] 0.93; 95% CI 0.38-2.27; P-value 0.87). Multivariate Cox proportion analysis, however, suggested that extramedullary relapse (HR 2.63; 95% CI 1.04-6.65; P-value <0.001), presence of high-risk cytogenetics (HR 6.6; 95% CI 1.82-24; P-value <0.001), and poor response to salvage regimens (<PR) (HR 7.48; 95% CI 2.27-24.7; P-value <0.001) predicted poor PFS. In MM patients relapsing post ASCT, we suggest that extramedullary relapse, presence of high-risk cytogenetics, and poor response to a salvage regimen, irrespective of salvage used, predict a poor PFS. However, these findings require validation by a randomized control trial.

Optimal timing of treatment at relapse after autologous stem cell transplantation in patients with multiple myeloma: a study of the Korean Multiple Myeloma Working Party (KMM-1909).

The effectiveness of early treatment for biochemical relapse of multiple myeloma (MM) is unclear. To clarify this issue, this retrospective study was performed to evaluate the survival outcomes of 315 patients with relapsed MM after upfront autologous stem cell transplantation (ASCT). Over a median follow-up of 66.6 months (range, 15.1-195.5 months), 48.2% of patients showed biochemical relapse, 41.3% showed clinical relapse, and 10.5% showed significant biochemical relapse. Progression-free survival (PFS) and overall survival (OS) were inferior for patients with clinical relapse compared to the other patients. Multivariate analysis showed that clinical relapse was an independent prognostic factor for OS. In patients with biochemical relapse, there was no significant difference in survival between patients treated while asymptomatic and those treated once clinical symptoms had appeared. Relapse type after upfront ASCT was a significant prognostic factor in patients with MM. In addition, no survival benefit of early treatment at biochemical relapse was observed, but a triplet regimen may be beneficial for MM patients with biochemical relapse.

Deepening Responses after Upfront Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction Therapy

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Achievement of complete response (CR) and minimal residual disease (MRD) negativity are associated with improved progression-free survival (PFS) and overall survival (OS). With superior triplet- and quadruplet-based induction regimens, a higher proportion of patients are achieving deep responses of at least a very good partial response (VGPR) or better. The probability of achieving different levels of deeper hematologic responses post-ASCT based on the pre-ASCT depth of response is less clear in the existing literature but would be of value to patients and providers in discussing the added benefit of ASCT. We assessed the rate of deepening the hematologic response with upfront ASCT in patients with NDMM, mainly to MRD-negative CR, based on the response achieved after induction therapy. We retrospectively reviewed 210 patients with NDMM who underwent upfront ASCT at Mayo Clinic Rochester between May 1, 2018, and July 31, 2019. In addition to the availability of next-generation flow cytometry (NGF) testing for MRD status, which yielded a sensitivity of 10-5, the more sensitive mass spectrometry-based assessment of peripheral blood (ie, MASS-FIX) for monoclonal proteins was used rather than conventional immunofixation. Pre-ASCT, 23 patients (11%) achieved MRD-negative CR, which increased to 66 patients (31%) post-ASCT. Of 187 patients not in MRD-negative CR pre-ASCT, 45 (24%) converted to MRD-negative CR. Patients with MRD-positive CR before ASCT had the highest rates of conversion to MRD-negative CR. HR cytogenetics did not impact rates of MRD-negative CR achievement post-ASCT irrespective of pre-ASCT IMWG response (P=1.0). Overall, irrespective of IMWG response, 43 patients (20%) were MRD-negative pre-ASCT (19 in VGPR, 24 in CR or sCR), and 102 patients (49%) were MRD-negative post-ASCT (36 in VGPR, 66 in CR or sCR). Among 85 patients with VGPR post-ASCT, 36 achieved MRD negativity, of whom 8 (22%) progressed, whereas 49 had MRD-positive disease, of whom 24 (49%) progressed (P=.014). Upfront ASCT in patients with NDMM led to deeper responses, with 24% converting to MRD negative CR and more than doubling of the total rate of MRD negativity irrespective of IMWG response depth.

Impact of autologous stem cell transplantation on survival outcomes in patients with peripheral T cell lymphoma

Data about the timing of autologous stem cell transplantation (ASCT) in peripheral T cell lymphoma (PTCL) are conflicting. We aimed to investigate the impact of the sequence of ASCT on the survival outcomes in patients with PTCL. Analyzes were performed retrospectively in a total of 81 patients, 16 of whom underwent upfront ASCT and 12 received salvage ASCT. In univariate analysis, upfront ASCT reduced the risk of progression and death by 77% (Hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.09–0.60) (p = 0.003) and by 84% (HR: 0.16, 95% CI: 0.5–0.55) (p = 0.003), respectively. However, in multivariate analysis, only salvage ASCT predicted a more favorable progression-free and overall survival (HR: 0.17, 95% CI: 0.06–0.48, p = 0.001 and HR: 0.20, %95 GA: 0.06–0.62, p = 0.005, respectively). In conclusion, regardless of first-line therapy, patients have more favorable outcomes if they receive salvage ASCT. Upfront ASCT does not add clinically significant benefit to survival outcomes.

PB1982: DEEPENING OF RESPONSE IN PATIENTS WITH MULTIPLE MYELOMA AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION: A MULTICENTRIC STUDY IN A LATINO POPULATION

Background: Over the last decades Multiple myeloma (MM) outcomes have shown a continuous improvement as novel drugs and maintenance therapy have been incorporated. However, availability of these resources is still limited in low- and middle-income countries (LMIC), where autologous stem cell transplant (ASCT) continues to be the best strategy to achieve better response and survival. Aims: Our aim was to analyze the deepening of response after ASCT and its impact over survival outcomes in newly diagnosed MM (NDMM) patients. Methods: Multicenter retrospective study that included patients ≥ 18 years of age with NDMM who received upfront ASCT as consolidation between 2015 and 2020 at six transplant centers in Mexico. Response after ASCT was defined as any improvement of response according to IMWG criteria. Novel agents were considered: proteasome inhibitors, immunomodulatory drugs, other than thalidomide, and monoclonal antibodies. Results: A total of 126 patients were included. The median age at diagnosis was 53.1 years (range 38-68) and 55% were male. Most common isotype was IgG (60.3%) and extramedullary disease was present in 12.2%. Regarding risk, 72.7% were classified as ISS ≥2 and 18.7% of patients evaluated had high-risk cytogenetics (n=64). Induction therapy with novel agents was administered to 77 patients (61.2%). Pre-ASCT, 73.1% had a very good partial response (VGPR) or better. Conditioning regimen was melphalan-based in 96%, with 15.9% being oral melphalan. Five patients received a tandem ASCT (4.0%) and 86 (68.3%) maintenance therapy, being thalidomide-based in 54.6%. Response after ASCT was evaluated in 86.5% (n=109), with an improvement of response in 27.5%. Patients with ≥VGPR were 82.5%. The median overall survival (OS) of the cohort was 119 months (90.0 – 149.34) and progression-free survival (PFS) was 67.1 months (61.3 - 72.8). Deepening and maintenance of response after ASCT were associated with a better OS, 119.7 vs. 63.0 months (p=0.017) (Figure 1). Image:Summary/Conclusion: This is the first multicenter study of a Latino population that reports the impact of transplant on response deepening and survival of NDMM patients. ASCT improved responses in almost 30% of our patients, being this related to an increased OS. It is of utmost importance to increase access to novel drugs in low- and middle-income countries, albeit ASCT continues to be the standard of care in patients with NDMM and demonstrated to be the best consolidation strategy to improve response and survival in our population and therefore its use should be promoted and expanded in LMIC.

P884: POTENTIAL BENEFIT OF POST-TRANSPLANT DOXYCYCLINE IN AL ACHIEVING HEMATOLOGICAL RESPONSE AFTER AUTOLOGOUS STEM CELL TRANSPLANT – LONG TERM FOLLOW UP

Background: Systemic light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by multiorgan deposition of fibrils composed of misfolded immunoglobulin light chains. Current treatment strategies targeting the plasma cell clone do not result in immediate organ recovery, and thus effective fibril-directed therapies are needed. Doxycycline has been shown to disrupt amyloid fibril formation in preclinical models. In 2012, we reported initial results on the impact of posttransplant prophylaxis with doxycycline using data from 445 AL amyloidosis patients; prophylaxis with doxycycline was associated with improved survival compared to penicillin in those achieving hematologic response. Since then, few studies have evaluated doxycycline use in AL amyloidosis, mainly in combination with induction chemotherapy, with mixed results. We provide here updated results on outcomes of AL amyloidosis patients who received doxycycline prophylaxis post autologous stem cell transplantation (ASCT) in our institution. Aims: To evaluate the impact of doxycycline use for post-ASCT antimicrobial prophylaxis on survival in AL amyloidosis patients. Methods: We included 553 patients who underwent ASCT from July 1996 to June 2014. We excluded patients who died within 100 days of ASCT. Doxycycline 100 mg daily was substituted for penicillin prophylaxis in patients with penicillin allergy; since 2013, doxycycline has become the standard for prophylaxis in AL amyloidosis at our institution. Prophylaxis was typically continued for a year after ASCT. Antibiotic type was determined by review of medical records. The Kaplan-Meier method was used to estimate time to next treatment (TTNT) and overall survival (OS), both measured from the time of transplant; curves were compared using the log-rank test. Results: Median age was 59 and 60% were male. The median time from diagnosis to ASCT was 4 months; 90% had early ASCT (within 1 year of diagnosis) and 57% received upfront ASCT without prior induction. Penicillin was used for prophylaxis in 67% (372 patients); the rest received doxycycline. Hematologic and organ response rates were similar in the 2 groups. Median follow up from ASCT was 10.5 vs. 13.6 years in the doxycycline and penicillin groups, respectively. Among patients with early ASCT, TTNT was 5.5 (95%CI: 4.2-8.1) vs. 5.8 (95%CI: 4.7-6.8) years, respectively (P=0.95). Median OS was 12.0 (95%CI: 11.0-19.6) vs. 11.0 (95%CI: 9.6-12.7) years, respectively (P=0.17); 5- and 10-year OS rates were 81% vs. 75% and 62% vs. 54% in the doxycycline and penicillin groups, respectively. Among patients with day 100 hematologic response, there was a non-statistically significant trend towards improved OS with doxycycline, but no difference in those without hematologic response: median OS with doxycycline vs. penicillin was 21.1 vs. 14.6 years in patients with day 100 dFLC <4 mg/dL (P=0.18) Figure 1a. In patients with normal day 100 FLCr, median OS was NR vs. 12.8 years, respectively (P=0.10) Figure 1b. There was no difference between the 2 groups when OS was stratified by Mayo 2012 stage (1-2 vs 3-4), number of involved organs (1 vs. >1), ASCT period (before or after 2012), or pre-ASCT induction (Yes vs. No). Image:Summary/Conclusion: After 13 years of follow up we observed a trend towards improved OS with doxycycline as post-ASCT prophylaxis in patients who achieve a hematological response. Prospective studies are needed to elucidate whether doxycycline improves outcomes in AL amyloidosis and identify the optimal dose, duration, timing, and the subset of patients likely to benefit.

Continuous induction with lenalidomide/dexamethasone versus autologous stem cell transplantation in newly diagnosed multiple myeloma: a case for response-adapted approach

Although upfront autologous stem cell transplantation (ASCT) generally improves progression-free survival (PFS) in newly diagnosed multiple myeloma (NDMM), the overall survival (OS) benefit and optimal timing of ASCT are not well established. Patients with early response may be able to safely continue induction and avoid ASCT without compromised outcomes. We report an extended follow-up analysis of a phase 2 trial that randomized transplant-eligible patients with NDMM who responded to induction (50/65 patients) to continued induction or ASCT; median follow-up was 8.0 years. Patients had similar 8-year PFS (55% vs. 43%), 8-year OS (83% vs. 72%), and rates of at least very good partial response (72% vs. 84%) whether continuing induction of lenalidomide and dexamethasone (Ld arm) or receiving ASCT (Ld + ASCT arm) (p = 0.5). Notably, over 50% of patients receiving continuous Ld had PFS of 5–10 years. These results suggest the need for prospective trials incorporating response-adapted therapeutic approaches to NDMM. STATEMENT OF PRIOR PRESENTATION Presented in abstract form (interim analysis) at the 56th annual meeting of the American Society of Hematology (San Francisco, CA, 6 December 2014) and at the 57th annual meeting of the American Society of Hematology (Orlando, FL, 3 December 2015).

Relapse with plasmacytoma after upfront autologous stem cell transplantation in multiple myeloma.

Plasmacytoma has been reported to be associated with a poor prognosis in patients with multiple myeloma (MM). In this study, we evaluated the incidence of relapse with plasmacytoma and survival outcomes after upfront autologous stem cell transplantation (ASCT). This study retrospectively analyzed the data of 303 patients with MM who underwent upfront ASCT between April 2000 and April 2018 at eight institutes in the Republic of Korea. In total, 52 patients (17.1%) had plasmacytoma at MM relapse after upfront ASCT, of whom, 27 had paramedullary plasmacytoma (PMD) and 25 had extramedullary plasmacytoma (EMD). Patients with initial plasmacytoma were more likely to have plasmacytoma at MM relapse than those without initial plasmacytoma (37.1% vs. 11.2%). Over a median follow-up of 66.0months, patients with plasmacytoma at relapse had significantly inferior overall survival (OS) than those without plasmacytoma (43.9 vs. 100.7months, P < 0.001), but the OS did not significantly differ between patients with EMD and those with PMD (42.2 vs. 56.6 months, P = 0.464). After MM relapse, all patients received salvage therapy, and progression-free survival after relapse was significantly shorter in patients with plasmacytoma than in those without (6.4 vs. 12.4months, P = 0.007). This study showed that plasmacytoma frequently developed at MM relapse after upfront ASCT in patients with plasmacytoma at the time of diagnosis. Plasmacytoma at relapse was significantly associated with a poor prognosis.

Impact of autologous transplantation on survival in patients with newly diagnosed multiple myeloma who have high-risk cytogenetics: A meta-analysis of randomized controlled trials.

Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk. All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I2 ) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test. After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I2 = 0%) and 0.66 (95% CI, 0.45-0.97; I2 = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I2 = 0%) versus 0.52 (95% CI, 0.33-0.83; I2 = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction = .25). The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation. Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.

Prognostic value of the Kyoto Prognostic Index in higher-risk diffuse large B-cell lymphomas treated by upfront autologous stem cell transplantation in JCOG0908 trial.

BackgroundThere is currently no standard prognostic model optimized for the patients with diffuse large B-cell lymphoma (DLBCL) treated with upfront intensive immunochemotherapy including autologous stem cell transplantation (ASCT). The Kyoto Prognostic Index (KPI) has been proposed as a novel prognostic model for DLBCL, which can accurately identify especially high-risk patients. In this study, we investigated the prognostic value of the KPI in JCOG0908 trial in which higher-risk DLBCL patients defined by the conventional International Prognostic Index (IPI) were treated with upfront high dose therapy followed by ASCT.MethodsFifty-eight patients with DLBCL, not otherwise specified, enrolled in JCOG0908 and confirmed by the central pathological review were analyzed. The Kaplan–Meier method was used to estimate the probabilities of overall survival (OS) and progression-free survival (PFS). We compared the discrimination ability of the KPI with that of the IPI.ResultsAccording to KPI, 3-year OS and PFS rates were 86.7% and 76.7% in low-intermediate, 73.3% and 60.0% in high-intermediate, and 61.5% and 46.2% in high-risk group. According to IPI, 3-year OS and PFS rates were 75.0% and 50.0% in low-intermediate, 82.9% and 74.3% in high-intermediate, and 63.6% and 54.5% in high-risk group. The concordance-indices of KPI and IPI were 0.642 and 0.580 for OS and 0.606 and 0.606 for PFS.ConclusionsThe KPI may be a suitable predictor of outcome than the IPI for patients with higher-risk DLBCL treated with upfront intensive immunochemotherapy including ASCT.

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.

Role of upfront autologous stem cell transplantation in patients newly diagnosed with primary CNS lymphoma treated with R-MVP: real-world data from a retrospective single-center analysis.

The role of upfront autologous stem cell transplantation (ASCT) remains unclear in patients with primary central nervous system lymphoma (PCNSL) receiving rituximab and high-dose methotrexate (MTX)-based chemotherapy. We analyzed the outcomes of upfront ASCT in 106 patients with PCNSL (median age, 64 years; range, 34-86) who received rituximab, MTX, vincristine, and prednisolone (R-MVP). The objective response rate was 88.7% (94/106) and included 46 complete responses (43.4%). Upfront ASCT was performed in 38 responders (median age, 51 years; range, 34-69), including 13 patients aged >60 years, after conditioning with busulfan (3.2 mg/kg, days 8 to 5) and thiotepa (5 mg/kg, days 4-3). For 56 responders ineligible for ASCT because of age >70 years, poor performance status, or refusal to undergo upfront ASCT, other consolidation treatments (n = 32) or observation (n = 24) were performed. With a median follow-up of 24.4 months (95% confidence interval, 20.7-28.0 months), no transplantation-related deaths occurred and seven patients relapsed after upfront ASCT. By contrast, 24 relapses occurred in patients who did not receive upfront ASCT. The progression-free and overall survival were significantly better in patients undergoing upfront ASCT (P = 0.001). Our real-world data suggest the benefit from upfront ASCT.

Current Frontline Treatment of Multiple Myeloma.

Treatment paradigms for management of newly diagnosed (ND) multiple myeloma have been evolving over the past 20 years as a consequence of the development of immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. While recent studies have continued to confirm the progression-free survival benefit of consolidation with upfront autologous stem cell transplant in those considered transplant eligible (TE), the line between induction strategies for TE and transplant-ineligible (TI) patients has blurred, based on studies evaluating both populations. Here, we present an overview of the data guiding current treatment approaches in the ND setting and discuss areas of ongoing investigation, including the role of quadruplet combination therapies in TE patients, the optimal strategies for frail TI patients, and management of high-risk disease.

Impact of Induction Therapy with VRD versus VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation

Bortezomib-based triplet regimens-specifically bortezomib, lenalidomide, and dexamethasone (VRD) and bortezomib, cyclophosphamide, and dexamethasone (VCD)-are the 2 most common induction regimens used in transplantation-eligible patients with newly diagnosed multiple myeloma (NDMM), with conflicting data on comparative efficacy and outcomes in this population. We compared long-term outcomes of patients with NDMM receiving VRD induction and those receiving VCD induction prior to autologous stem cell transplantation (ASCT). Patients registered with the Center for International Blood and Marrow Transplant Registry were included if they had undergone ASCT for MM within 6 months of diagnosis between January 2013 and December 2018, received VRD or VCD induction, and achieved a pretransplantation partial or better response. Of 1135 patients, 914 received VRD and 221 received VCD. The patients receiving VCD were more likely to have renal impairment and International Staging System (ISS) stage III disease and less likely to receive full-dose melphalan (200 mg/m2) conditioning (69% versus 80%; P < .001). Very good partial response rates pretransplantation, post-transplantation, and at best response were not significantly different in the 2 groups. Maintenance use was more common after VRD induction (88% versus 76%; P < .001), with lenalidomide the most common agent (80% versus 63%). Patients in the VRD group had a higher rate of renal recovery (74% versus 43%; P < .001), possibly due to a rapid reduction of light chains in the VRD group or improvement in renal function with VCD, which allowed a switch over to VRD, as patients who switched were classified in the VRD group. Patients receiving VRD had better survival on univariate analysis, with a median progression-free survival (PFS) from transplantation of 44.6 months versus 34.1 months (P=.004) and median 5-year overall survival (OS) of 79% versus 60% (P < .001). Multivariate analysis showed no significant survival difference, with a hazard ratio for VCD versus VRD induction of 1.22 (95% CI, 0.96 to 1.55; P=.10) for PFS and 1.33 (95% CI, 0.93 to 1.92, P=.12) for OS. Maintenance use was independently associated with superior PFS and OS, along with ISS stage, cytogenetics, and pretransplantation response (PFS only). In patients with MM undergoing upfront ASCT after VRD or VCD induction, no independent survival difference was seen based on the induction therapy received after adjusting for other prognostic factors. The use of maintenance treatment was uniformly associated with superior outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Outcomes Following Biochemical or Clinical Progression in Patients with Multiple Myeloma

Outcomes Following Biochemical or Clinical Progression in Patients with Multiple Myeloma

Prognostic Factors for Early (5 years) Relapse in Multiple Myeloma- Pivotal Role of Cytogenetic Changes

Prognostic Factors for Early (<2 years) and Late (>5 years) Relapse in Multiple Myeloma- Pivotal Role of Cytogenetic Changes

Inferior Outcomes for Multiple Myeloma (MM) Patients (pts) Harbouring t(11;14) and the Promise of Venetoclax, Real-World Australian Retrospective

Introduction/ BackgroundTraditionally, MM harbouring t(11;14) is considered standard risk disease. In the era of novel therapies, however, pts with t(11;14) are reported to have inferior outcomes to other standard risk pts. Evidence of response to the BCL-2 inhibitor, Venetoclax (Ven), has further increased interest in understanding outcomes of t(11;14) pts. In this study, we aimed to describe the historical outcomes of t(11;14) MM and response to Ven in a real-world cohort of Australian pts.MethodsThis was a retrospective, multicentre study conducted by members of the Australasian Leukaemia and Lymphoma Group, Myeloma Working Party. Cases were identified by interrogation of cytogenetics/FISH database from 2010 to 2019 inclusive. Baseline patient and disease characteristics, treatment exposure and outcomes were extracted from hospital medical records. Descriptive statistics, and survival analyses were performed as appropriate.ResultsSeventy-four pts [median age 65 years (yrs), range (43-85)] were identified across seven centres. 43% pts had ISS Stage III MM with 88% harbouring additional cytogenetic abnormalities, incl. 13% with gain in 1q and 12% with del(17p). The majority (81%) of pts received proteasome inhibitor (PI)-based 1 st line therapy with 60% having an upfront autologous stem cell transplant (ASCT) and 54% having immunomodulatory drug (IMiD)-based maintenance therapy. Two patients received an allogeneic stem cell transplant after ASCT. The overall response rate (ORR) was 86% with 38% achieving very good partial response (VGPR) or better. The median progression free survival-1 (PFS-1) was 1.91 yrs (95% CI 1.73-2.56) [PI-based, n=60, PFS 1.84yrs (95% CI 1.61-2.41) vs IMiD-based, n=5, PFS 4.58yrs (95% CI 1.16-5.51), HR 0.68 p=0.45] The median overall survival (OS) was 5.35 yrs (95% CI 4.12-6.56). Second and third line therapy was predominantly IMiD-based (see Table 1) with recent introduction of anti-CD38 monoclonal antibodies (mAbs). Median PFS-2 was 0.77 yrs (95% CI 0.39-0.98) while median PFS-3 was 0.65 yrs (95% CI 0.34-1.16). Eleven pts (median 3 prior lines of therapy) were given Ven [Six pts in combination with PI, three with PI and mAbs and two with dexamethasone]. ORR to Ven was 55% with 45% achieving VGPR or better. Median PFS with Ven was 0.54 yrs (85% CI 0.05-2.17). Median PFS for patients with 1-4 lines (n=6) was 1.22 years and median PFS for patients with 5 lines or more (n=5) was 0.54 years, HR 0.56 (95% CI 0.12-2.5).ConclusionFor pts harbouring t(11;14), the duration of response to PI-based 1 st line therapy is suboptimal even with the use of ASCT consolidation in the majority of patients. Despite multiple prior lines of therapy, Venetoclax shows promising results and every effort should be made for early identification of this cytogenetic lesion. Further studies are required to examine the impact of novel triplet and quadruplet combination therapy and use of venetoclax early in the disease course of this sub-group of patients. [Display omitted] DisclosuresTalaulikar: Takeda: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Roche: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Gibbs: Janssen, Celgene, Amgen, Takeda, BMS and Pfizer: Consultancy, Honoraria; AbbVie: Consultancy.

Upfront Autologous Stem Cell Transplantation (ASCT) Vs Carfilzomib-Cyclophosphamide-Dexamethasone (KCd) Consolidation in Transplant-Eligible, Newly Diagnosed (NDTE) Multiple Myeloma (MM): Results of the Cardamon Study According to Cytogenetic Risk

Upfront Autologous Stem Cell Transplantation (ASCT) Vs Carfilzomib-Cyclophosphamide-Dexamethasone (KCd) Consolidation in Transplant-Eligible, Newly Diagnosed (NDTE) Multiple Myeloma (MM): Results of the Cardamon Study According to Cytogenetic Risk

Second Line Treatment Strategies in Multiple Myeloma: A Referral-Center Experience

Second Line Treatment Strategies in Multiple Myeloma: A Referral-Center Experience