Autologous Transplantation For Multiple Myeloma Research Articles

Use of Hematopoietic Cell Transplant for Hematologic Cancers by Race, Ethnicity, and Age.

Utilization of hematopoietic cell transplantation (HCT) for hematologic cancers previously demonstrated race, ethnicity, and age-based disparities. To evaluate utilization over time by race, ethnicity, and age to determine if disparities persist in light of recent significant increases in HCT volume. This US population-based retrospective cohort study includes patients who received transplants from January 2009 to December 2018. Data collection and cleaning occurred from February 2019 to November 2021, and data analysis occurred from January 2022 to October 2023. Method 1 restricted the analysis to Surveillance, Epidemiology and End Results (SEER) reporting areas for cases and transplants. Method 2 applied SEER age-, race-, and ethnicity-specific incidence rates to corresponding US census population and included all transplants reported to the Center for International Blood and Marrow Transplant Research. Race and ethnicity groups were hierarchically defined as Hispanic (any race), non-Hispanic White, non-Hispanic Black, and non-Hispanic Other (Asian and American Indian). Receipt of HCT. Utilization rate of autologous or allogeneic HCT for patients with hematologic cancers by age, race, and ethnicity. From 2009 to 2018, 136 280 HCTs were analyzed for 6 hematologic cancers comprising 16.7% pediatric/adolescent/young adults (0-39 years), 83.3% adults (40-84 years), 58% male, 10.3% Hispanic, 11.4% non-Hispanic Black, 3.8% non-Hispanic Other, and 74.5% non-Hispanic White patients, with 49 385 allogeneic and 86 895 autologous HCTs performed. HCT utilization increased over time for all disease, age, race, and ethnic groups. From 2017 to 2018, adult (40-84 years) allogeneic transplant utilization for acute myeloid leukemia and myelodysplastic syndrome (MDS) was similar for Hispanic and non-Hispanic White or Other patients but was lower for non-Hispanic Black patients (acute myeloid leukemia: 19% vs 13%; MDS: 9%-10% vs 5%). Similarly, autologous transplant utilization for lymphoma was similar for all race and ethnicity groups; however, autologous transplant for multiple myeloma was highest for non-Hispanic White patients and lower for all other groups (31% vs 26%-27%). In patients aged 0 to 39 years, utilization of allogeneic transplant for acute lymphoblastic leukemia was highest in Hispanic patients, followed by non-Hispanic White, Black, and Other races (acute lymphoblastic leukemia: 19%, 18%, 17%, and 16%, respectively). In this cohort study of autologous and allogeneic transplant utilization for hematologic cancers, disparities persisted for non-Hispanic Black patients. Hispanic, non-Hispanic Other, and younger age groups had increased utilization over time that was on par with non-Hispanic White patients in the most recent cohort.

Trends in Outcomes After Upfront Autologous Transplant for Multiple Myeloma Over Three Decades

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (P < .001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (P < .001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, P < .001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, P < .001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, P = .001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, P < .001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, P < .001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM undergoing upfront auto-SCT over the past three decades, including those with high-risk disease.

Artificial Intelligence Enabled ECG Interpretation Informs Outcomes after Autologous Transplantation for Multiple Myeloma

High dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) is a standard therapy for patients with plasma cell disorders (PCD). A barrier to improving candidate selection for auto HCT is appraisal of risk for transplant related complications. Electrocardiography (ECG) is a standard pre-HCT test to evaluate the potential for arrhythmia and structural heart disease. We hypothesized that an artificial intelligence (AI) based interpretation of ECG waveform data (AI-ECG) could enhance risk prediction for cardiac-specific and other outcomes following auto HCT for patients with PCD. To test this hypothesis, we used several AI-ECG tools developed using a deep-learning based approach that were trained to predict comorbidity (Attia et al, Lancet 2019 &amp; Grogan et al, Mayo Clin Proc 2021). Model outputs include a scaled prediction value indicating increasing risk for atrial fibrillation/flutter (AF), reduced ejection fraction (EF), or cardiac amyloidosis. We evaluated this tool in 9,225 ECGs obtained from 849 patients (median 6 ECGs/patient, inter-quartile range: 3-12) who underwent first or subsequent auto HCT at Memorial Sloan Kettering Cancer Center between 2016-2022 and who had a diagnosis of multiple myeloma (N = 810), amyloidosis (N = 37), or other PCD (N = 2). The endpoints were to determine whether baseline AI-ECG prediction of AF risk correlated with peri-transplant AF events, and to explore whether model outputs correlated with survival and other cardiac clinical outcomes. The mean age of patients was 61.0 years (range 23.7 - 81.2) and median follow up was 2.7 years post auto HCT. Contributing cardiovascular risk factors included a prior history of AF (N = 101, 11.9%), coronary or cerebrovascular disease (N = 95, 11.2%), and diabetes mellitus (N = 98, 11.5%). Reduced dose melphalan (&amp;lt; 200 mg/m 2) was administered in 26%. The HCT-comorbidity index (HCT-CI) was high risk (≥3) in 52.7%. The one-year overall survival and progression-free survival in the whole cohort was 94% (95% confidence interval (95% CI): 92 - 95%) and 86% (84 - 89%), respectively. Among patients not in AF at pre HCT evaluation, the 90-day cumulative incidence of AF was 5.6% (4.2 - 7.3%). In univariable competing risk regression, baseline pre HCT AI-ECG appraisal of AF risk was strongly correlated with incidence AF in patients who were in sinus rhythm before HCT (hazard ratio (HR): 25.1, 95% CI: 11.7 - 53.7, p &amp;lt; 0.001). In a multivariable model adjusting for patient age and HCT-CI, AI-ECG AF predicted risk remained associated with incidence of post HCT AF (HR: 13.4, 95% CI: 5.9 - 30.4, p &amp;lt; 0.001). Considering a decision threshold identified during original model training, AI-ECG predicted AF events with an accuracy of 75% (Mcnemar's p &amp;lt; 2 x 10 -16). The precision, recall, and F1-score were 0.94, 0.77, and 0.85, respectively. AI-ECG predicted age correlated highly with actual patient age (Spearman rho = 0.59, p &amp;lt; 2 x 10 -16). Amyloid risk scores were highly correlated with a known clinical history of amyloidosis (median 0.45 versus 0.05, Wilcoxon rank-sum p &amp;lt; 0.001). Patients with EF &amp;lt; 50% had greater prediction scores for cardiomyopathy compared to patients with normal EF (median 0.23 versus 0.01, Wilcoxon rank-sum p &amp;lt;0.001). In univariable analysis, increasing AI-ECG predicted age (HR 1.02, CI: 1.003 - 1.04, p = 0.02) and predicted AF risk score (HR: 3.2, CI: 1.4 - 7.2, p = 0.006) were associated with risk for death, whereas predicted amyloid score and predicted low EF were not associated with decreased survival. In multivariable analysis of all patients that considered patient age, hematopoietic comorbidity index, and remission status at HCT, increasing predicted AF score trended towards association with increased risk for death (HR: 2.3, 95%CI: 1.0 - 5.5, p = 0.059). Predicted AF score correlated highly with the HCT-CI and patient age. Finally, we examined whether risk prediction for low EF correlated with peri-HCT fluid overload (FO) defined by absolute weight gain. The incidence of ≥ 10% weight gain (grade 2 FO) and ≥ 20% weight gain (grade 3 FO) at 180 days post HCT was 7.4% (95% CI: 5.8%, 9.3%) and 1.0% (95% CI: 0.5%, 1.8%), respectively. Predicted low EF was not associated with development of either grade 2 or grade 3 FO in this population. In summary, AI-ECG predicts episodes of AF in patients undergoing auto HCT for PCD and may augment transplant risk appraisal when considered in conjunction with other measures of comorbidity.

Continuous Elotuzumab, Pomalidomide, and Dexamethasone Maintenance Following Second Autologous Transplantation for Multiple Myeloma: Results of a Prospective Phase 2 Multicenter Trial

Second autologous hematopoietic cell transplantation (AHCT2) is a useful therapeutic modality for fit patients with multiple myeloma who have durable remission after upfront AHCT. Retrospective studies have suggested a significant benefit of incorporating maintenance therapy post-AHCT2, but prospective data on specific regimens are lacking. The purpose of this study was to investigate the use of elotuzumab, pomalidomide, and dexamethasone (EPd) as salvage therapy prior to and maintenance after AHCT2 for relapsed multiple myeloma. This prospective single-arm phase II trial investigating the use of EPd in combination with AHCT2 in patients with relapsed multiple myeloma was conducted at 2 academic centers in North America. The primary outcome was 1-year progression-free survival (PFS). Twenty-five patients were enrolled on the study. Sixteen patients received EPd induction; six patients (38%) progressed during salvage therapy and were removed from the trial prior to AHCT2. Following a planned safety analysis, the protocol was amended, and EPd induction was removed from the study schema. An additional 9 patients underwent induction off-study and were enrolled on trial for AHCT2 and EPd maintenance. A total of 18 patients underwent AHCT2 and received EPd maintenance. Two patients discontinued treatment because of toxicity, one attributed to elotuzumab and the other to pomalidomide. The 1-year PFS was 72%, and the median PFS was 19 months. The study was closed early owing to poor accrual; 6 patients remained on therapy at time of analysis. EPd maintenance after AHCT2 was safe and tolerable. The 1-year PFS and median PFS were similar to values in previous retrospective reports of outcomes following AHCT2. Further studies are needed to define the optimal use of and protocol for AHCT2 in fit patients with relapsed multiple myeloma.

The Impact of CD34+ Cell Collection Yields for Autologous Transplant on Survival Outcomes in Multiple Myeloma

IntroductionAccording to previous data, higher yields of stem-cells collected to support autologous transplantation may predict for improved outcomes. We aimed to assess the association between high stem-cells collection and survival outcomes in multiple myeloma (MM) Materials and MethodsWe reviewed all patients who underwent autologous transplantation for MM at our center over a 10-year period, and initially used a predefined threshold of 8 × 106/kg used in previous studies. ResultsSix hundred twenty-one patients were analyzed. Higher mobilization did not correlate with favorable outcomes post-transplant. The most efficient mobilizers, collecting ≥8 × 106/kg (n = 478) achieved a shorter median progression-free survival (PFS) of 24.1m versus 34.5m in patients collecting 4.5 to 8 × 106/kg (n = 129). A small group (n = 14) collecting ≤4.5 × 106/kg but minimum of 2 × 106/kg to support autologous transplantation exhibited the worst outcomes (median PFS 11.4m). Further analysis of potential confounders identified greater use of bortezomib induction in the lower mobilizers, however, sensitivity analysis in patients receiving bortezomib revealed similar results- worst outcomes to the most efficient mobilizers. ConclusionAlthough bortezomib is not considered stem-cell toxic, it may be associated with lower stem cell collection yields. Bortezomib's efficacy at induction may partially explain the improved outcomes, however, other factors may be involved, and are discussed. We can conclude that with our large cohort and long follow-up, high stem-cell mobilization does not appear to predict for a long-term survival advantage.

Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34+ hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 106 CD34+ cells kg–1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12–201.33, P < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36–549.35, P < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov, NCT03246529

531 - Elotuzumab, Pomalidomide and Dexamethasone Maintenance after Salvage Second Autologous Transplant for Multiple Myeloma

531 - Elotuzumab, Pomalidomide and Dexamethasone Maintenance after Salvage Second Autologous Transplant for Multiple Myeloma

Alternating the Administration of Ixazomib and Lenalidomide As Maintenance Therapy after Autologous Transplant for Multiple Myeloma

Autologous transplant (ASCT) can cause remissions in Multiple Myeloma (MM) patients (pts), but relapse remains a major problem. Currently, lenalidomide alone for as long as tolerated post ASCT is the standard maintenance utilized in the USA. Since the use of an alternating schedule of an Immunomodulatory drug (IMiD) with a proteasome inhibitor (PI) might decrease the emergence of resistant dominant clones, we designed a study to investigate treating with a regimen alternating IMiD lenalidomide with PI ixazomib post ASCT. We report here on the toxicity and efficacy of this all-oral maintenance regimen. Thirty to 120 days after recovery from toxicity of ASCT, pts began study therapy. Treatment regimen consisted of alternating ixazomib 4mg po on days 1, 8 and 15 per each 28-day cycle for two consecutive cycles followed by lenalidomide 10mg po daily for two consecutive cycles until MM progression, intolerable toxicity or maximum of 24 cycles. Dose adjustment for toxicity occurred. Pts remained on anti-VZV and PJP prophylaxis throughout therapy and until 2 months after stopping therapy. Pts got bisphosphonate therapy. Pts also received DVT prophylaxis therapy as clinically indicated. The primary endpoint was toxicity. Secondary endpoints were ability to deliver planned therapy, initial response, overall progressive free and survival rates. Thirty pts were enrolled and treated on the study with at least 1 cycle of therapy. Twenty-three pts were male (77%), 13% were members of minority groups. The median age was 60 years (range 44-70 years). Three pts (10%) were over 65 years old. Fourteen pts (47%) had high-risk cyclogenetic MM per IMWG, including 6 pts (20%) that had multiple high-risk changes. Pts started study therapy at a median 107.5 days post ASCT (range 53-120 days). Thirteen pts (43%) stopped therapy before completing 24 cycles for the following reasons: relapse (n=8), patient's decision (n=2), secondary cancer treatment (n=1) and elective surgery that was complicated by infections (n=2). No pts met stopping rules for toxicity in the first 4 months of therapy. There were no deaths due to study therapy. The most common AE grades (gr) 2-4 were: abnormal glucose (10%, 100% gr 2), lymphocyte decreased (70%, 37% gr 2, 33% gr 3), low phosphate (17%, 100% gr 2), WBC decreased (53%, 33% gr 2, 20% gr 3), Platelet (PLT) decreased (33%, 23.3% gr 2, 6.7% gr 3 and 3.3% gr 4), ANC decreased (60%, 30% gr 2, 23.3% gr 3, 6.7% gr 4). The following infectious episodes were also seen in 27 patients (90%): non-identified upper respiratory tract infection (URTI) (n=34), identified URTI (n=9, included metapneumovirus (n=1), rhinovirus (n=2), RSV (n=1), influenza A (n=1) parainfluenza (n=2), RSV and COVID-19 (n=1) and COVID-19 (n=1)), nonneutropenic fever (n=1), thrush (n=1), conjunctivitis (n=1), shingles (n=1), cellulitis (n=3 include one case of MRSA), giardia (n=1), strep pneumonia with sepsis (n=1), bacterial pneumonia (n=2), viral gastroenteritis (n=2), urine tract infection (n=1), bronchitis (n=2) and tinea of the skin (n=1). The most frequent gr 3-4 AEs were hematological, with decreased WBC in 20%, decreased PLT in 10% and decreased ANC in 30% of pts. Twenty-four (80%) of the pts still had detectable MM disease after ASCT before starting study therapy. At completion of study therapy, 29.2% had progressed, 21% had stable disease, 4.2% were in PR, 29% in nCR, 8.3% in sCR and 8.3% in CR. Overall, 50% of patients converted to a deeper response (≥ PR). Four pts have developed a secondary cancer, localized skin cancer (n=3) and metastatic lung cancer (n=1). Only 1 pt was still receiving study therapy when the secondary cancer developed. Median follow-up is 3.95 years (range 3.18-6.7 years). Sixteen (53%) of the pts have relapsed. Eight pts (37%) have died including 6 pts with relapsed MM and 2 pts without relapse (metastatic lung cancer (n=1) and non-COVID infection (n=1). To date, 9 pts (30%) are alive in relapse and 13 pts (43%) are alive in remission. Post ASCT, the all oral regimen of alternating ixazomib and lenalidomide is overall well tolerated and has high initial response rates. Hematological toxicity as expected was the most significant toxicity. Significant gastrointestinal and peripheral neuropathy toxicity were not seen. The most common infection was non-specified URTI. A larger randomized trial comparing the alternating oral med schedule of ixazomib and lenalidomide to single agent lenalidomide is warranted.

The Landscape of Maintenance Therapy Trials Following Autologous Transplant for Multiple Myeloma

BACKGROUND: The current standard for maintenance therapy following autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) is lenalidomide, an oral treatment with demonstrated overall survival benefit. Other options for MM may incur toxicities or require frequent visits to infusion centers and may thus not be best suited as maintenance. Patients with high-risk cytogenetic features have poorer outcomes than those considered to have standard risk disease, and national guidelines recommend doublet maintenance (with a proteasome inhibitor and lenalidomide in this setting). Currently, the role of minimal residual disease (MRD) in treatment decision making is unknown but MRD status in this setting may dictate treatment discontinuation in the future. We conducted a review of currently enrolling clinical trials to characterize therapeutic agents/strategies being used or evaluated in a maintenance setting, outcomes evaluated, the inclusion of high-risk patients, and the use of MRD response in guiding management decisions. METHODS: A comprehensive search was performed on the clinicaltrials.gov, clinicaltrialsregister.eu, and anzctr.org.au databases on March 2, 2022, using the keywords "newly diagnosed multiple myeloma", "transplant eligible multiple myeloma", and "maintenance in multiple myeloma". Only studies that were currently recruiting patients, or those listed as active but not yet recruiting were included. Studies that completed enrollment, were terminated, or had been presented or published were not included. Studies were included if patients were planned to undergo autologous stem cell transplant after induction therapy followed by maintenance strategy. If at least one arm received post-transplant maintenance therapy, and the maintenance therapy was specified in the trial description, it was included. Trials evaluating maintenance therapy after a salvage transplant or maintenance therapy in non-transplant settings were excluded. RESULTS: A total of 20 studies were analyzed. Table 1 highlights characteristics. Of the 20 studies, 11 (55.0%) were randomized and 9 (45.0%) were non-randomized. Six studies (30.0%) evaluated PFS as a primary outcome, and 2 studies (10.0%) included OS as a primary outcome. Four of the 20 (20.0%) studies included multiple primary endpoints in addition to time to event outcome, while 4 (20.0%) had a time to event outcome as the sole primary outcome being investigated. Of the 11 randomized studies, 2 studies evaluated OS (18.1%) and 5 evaluated PFS (45.5%) as primary endpoint. MRD negativity was included as a primary endpoint in 11 studies (55.0%) and a secondary endpoint in seven (35%). Of the 9 nonrandomized studies, 4 had a primary endpoint of MRD negativity rate (44.4%), 2 (22.2%) had response-based primary outcomes, and one (11.1%) had a time to event primary outcome. Of the total trials, two (10.0%) assessed or mandated discontinuation of maintenance therapy for those achieving MRD negativity. Table 2 describes maintenance regimens utilized. A total of 4 randomized studies assessed comparison of lenalidomide and another agent to lenalidomide alone with a primary endpoint powered for PFS/OS. Only one study limited enrollment to standard risk disease. No studies enrolled only "high-risk" disease. Amongst a total of 19 trials enrolling patients with high-risk disease, eight trials (42.1%) were offering or permitting patients with high-risk disease to receive single agent lenalidomide. CONCLUSION: Our study analyzing the landscape of current maintenance trials demonstrates that there are many promising clinical trial designs that adapt treatment based on the depth of responses and incorporate newer agents with enough statistical power to demonstrate OS advantage. However, there remains room for improvement, as evidenced by trials evaluating drugs with marked toxicity profiles in non-randomized single arm settings, patients with high-risk disease being permitted to receive treatment that may be inferior to what current guidelines recommend, and a lack of patient centered endpoints (such as OS or quality of life) being evaluated as primary endpoints. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mathematical Models for Early Detection of Relapse in Multiple Myeloma Patients Treated with Bortezomib/Lenalidomide/Dexamethasone

Background: Multiple Myeloma (MM, an incurable bone marrow plasma cell malignancy, is the second most common hematological malignancy in the United States. The introduction of novel triplet-based induction therapy with bortezomib (Bor), lenalidomide (Len), and dexamethasone (Dex) has shown excellent results in several large, randomized phase III trials and is considered a standard of care for newly diagnosed MM (1-3). The question lies at which timing a clinician should move from VRd combination therapy to auto-HCT and sequential second-line therapy. Guidelines recommend waiting for International Myeloma Working Group Uniform Response Criteria (IMWG Criteria) to be met before proceeding to the next line of therapy. A tool to anticipate progression before IMWG Criteria may allow early switch to the next line therapy while the disease burden is relatively low (4). We aimed to evaluate predictive accuracy of a mathematical model to anticipate relapse 6 months before the IMWG Criteria are met. Methods: Four hundred seventy patients initially treated with a subset of VRd and with ≥ 3 serum M-protein values prior to auto-HCT, including one baseline value ≥ 0.5g/dL in the CoMMpass study (IA16) and were randomly split 2:1 into training and testing sets. A model of M-protein dynamics was developed using the training set. By fitting the model to each observation window in the testing set, distribution of future response trajectories was created for the whole population utilizing Bayesian parameter estimation, and by combining all the M-protein estimated trajectories, Receiver Operating Characteristics (ROC) curve was generated. As a comparator, we also tested most M-protein "velocity" through the two most recent time points as a predictor. Results: The two-population tumor growth inhibition model with additive drug effect and transit model for cell killing was identified to be the best model for both training and testing set. The model identified baseline R-ISS staging on M-protein baseline (M0), 1st response treatment outcome of first 2 cycles, which we will gain information before 3 months protein value data are gained, on frequency of resistant cell population (ϕ), and existence of t(4;14) mutation-positive cells on resistant cell function (dRes/dt) as the best predictor of serum M-protein kinetics. The ROC area under the curve (AUC) value of relapse prediction 180 days ahead of observed relapse by FPC was 0.829 with sensitivity and specificity both of 78% using an observation time of least 360 days, which was superior to the M-protein velocity ROC score of 0.713 under the same conditions (Fig 1B). ROC AUC continues to improve, and maintains its advantage over M-protein velocity, with each additional 90 days of observation time. Conclusion: The individualized model-based approach from data within the first 9 or more months of VRd treatment could provide prospective and reasonable predictions of future M-protein trajectories in individuals with MM. It allowed predictions for personalized "progression free" curve under various treatment scenarios. This model may enable a future study testing the difference in patient outcomes when treatment is switched when relapse is imminent versus already occurred. Reference: (1) Rosiñol, L. et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood134, 1337-45 (2019). (2) Durie, B.G.M. et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet389, 519-27 (2017). (3) Attal, M. et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med376, 1311-20 (2017). (4) Jackson, G. et al. Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol.6, e616-29 (2019). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma.

Autologous stem cell transplantation is the standard procedure for multiple myeloma and the grafts are usually cryopreserved. Previous studies reported advantages in the use of fresh peripheral blood stem cells (PBSC) autotransplantation compared to cryopreservation of the grafts. This study compared the transplant-related outcomes of two graft preservation methods: fresh storage (4°C/72 h) and cryopreservation (-80°C). We performed an analysis of 45 patients with multiple myeloma under autotransplantation (17 fresh and 28 cryopreserved) from 2017 to 2021. Fresh PBSC were maintained in the refrigerator for three days in a concentration up to 300 × 103 TNC/μL. Cryopreserved PBSC were concentrated by plasma reduction after centrifugation (950 g/10min/4°C) and an equal volume of cryoprotection solution was added for a final concentration of 300 × 103 TNC/μL, 5% DMSO, 6% hydroxyethyl starch, and 3% human albumin. Neutrophil engraftment was significantly faster with fresh PBSCs (10 vs. 11.5 days, p=0.045). Adverse effects were more common in cryopreserved PBSC transplantation (75% vs. 35.3% patients; p=0.013). Post transplantation hospital stay was 20 and 22 days for fresh and cryopreserved PBSCs respectively (p=0.091). There was no difference in platelet engraftment time (10.5 days for both; p=0.133), number of antibiotics used after transplantation (3 for fresh and 2.5 for cryopreserved; p=0.828), days of antibiotic use after transplantation (12.2 days for fresh and 13.3 days for cryopreserved, p=0.579), and overall survival (p=0.736). The infusion of fresh PBSC refrigerated for up to three days is effective and safe for autologous transplantation in patients with multiple myeloma, which is a useful alternative to cryopreserved PBSC.

High-Dose Bendamustine, Etoposide, Cytarabine, and Melphalan (BeEAM) Conditioning Before Autologous Transplantation for Patients With Multiple Myeloma

Single-agent high-dose melphalan (Mel) followed by autologous stem cell transplantation (ASCT) remains a standard of care in eligible patients with multiple myeloma (MM), and efforts to improve transplant outcomes by intensifying transplant conditioning have mostly failed. Bendamustine combines both alkylating and antimetabolite properties, can induce responses in MM resistant to other alkylators and represents a promising agent to combine with Mel prior to ASCT. We performed a phase II study to test the safety and efficacy of the high-dose chemotherapy combination of bendamustine, etoposide, cytarabine, and melphalan (BeEAM) in newly diagnosed MM patients up to 70 years of age. The primary study endpoint was the day 100 complete response rate. Sixty-five patients with a median (range) age of 59 (40-69) years underwent transplantation from 2015 to 2020. Other characteristics included Karnofsky performance status <80%, hematopoietic cell transplantation-comorbidity index ≥3, International Staging System III, and high-risk fluorescein in situ hybridization (FISH) in 35%, 46%, 26%, and 44%, respectively. ASCT after BeEAM was well tolerated, and there were no non-relapse deaths through 1 year after transplantation. Although at least 1 nonhematologic grade 3 toxicity was reported in 58 (89%) patients (including grade 3 febrile neutropenia in 48% and stomatitis/esophagitis in 28%), there were no grade ≥3 renal or hepatic toxicity and no grade ≥4 non-hematologic toxicity. The day 100 response rate was ≥CR1 and ≥ very good partial response (VGPR1) in 40% and 89%, respectively. With a median follow-up of 44 (13-70) months, the 3-year overall survival was 92%, 96%, and 90% for all patients and those with standard- and high-risk FISH, respectively. The corresponding values for 3-year progression-free survival was 57%, 72%, and 40%, respectively. When BeEAM-conditioned patients were compared to historical Mel-conditioned cohort, no significant differences were noted in relapse or survival outcomes in univariate or multivariable analysis. In summary, BeEAM was shown to be a safe and effective conditioning regimen before up-front autologous transplant for MM. Although the BeEAM regimen does not appear to offer a significant advantage over single-agent Mel, further studies combining bendamustine and melphalan in the front-line setting may be warranted.

High-Dose Bendamustine, Etoposide, Cytarabine and Melphalan (BeEAM) Conditioning Prior to Autologous Transplantation for Patients with Multiple Myeloma: Results of a Prospective Phase II Trial

Single-agent high-dose melphalan followed by autologous stem cell transplantation (ASCT) remains a standard of care in eligible patients with multiple myeloma (MM). Efforts to improve transplant outcomes by intensifying transplant conditioning have mostly failed, with the exception of a sole phase III study showing improved progression-free survival (PFS) with the addition of busulfan to melphalan (Lancet Haematology 2019, 6:266-75). Bendamustine is a synthetic agent that combines the alkylating properties of a mustard-group with the antimetabolic activity of a purine analog. It can induce responses in MM resistant to other alkylators and is therefore a promising agent to test synergy in conditioning regimens. The high-dose chemotherapy combination of bendamustine, etoposide, cytarabine and melphalan (BeEAM) has been shown to be a safe and effective transplant regimen for lymphoma patients (Blood 2011, 118:3419-25). We performed a phase II study to test the safety and efficacy of BeEAM in MM patients, 18-70 years of age, with adequate organ function (EF≥40% predicted, CrCl ≥40ml/min) and within 9 months of starting induction therapy. Results were compared to a contemporaneously treated control group receiving a single high-dose melphalan 200mg/m2 transplant (Mel200) but otherwise meeting study eligibility criteria. Study patients (n=65) had a median (range) age of 59 (40, 69) years and were transplanted from 2015-2020. Other characteristics included KPS<80%, HCT-CI≥3, ISS III, and high-risk FISH in 35%, 46%, 26% and 44% respectively. Pre-BMT status was (s)CR1, VGPR1, PR1 and <PR1 in 26%, 43%, 26% and 5% respectively. ASCT following BeEAM was well tolerated with no non-relapse deaths through one-year post-transplant. Although at least one non-hematologic grade 3 toxicity was reported in 32 (49%) patients, there were no grade ≥3 renal or hepatic toxicity and no grade ≥4 non-hematologic toxicity. With a median f/u of 44 (13, 70) months, three-year OS and PFS was 92% and 57% respectively. When BeEAM patients were compared to contemporaneously treated Mel200 patients, there were no significant differences in baseline characteristics, induction regimen or use of post-transplant maintenance therapy. Neutrophil and platelet engraftment was faster following BeEAM (11 vs. 12 days, 17 vs 18 days, p<0.001 and p=0.007 respectively), when compared to Mel200 patients. One-year non-relapse mortality was 0% with both BeEAM and Mel200. No significant differences were seen in quality of response, PFS or OS between BeEAM and Mel200, when analyzing either the whole cohort (see figure) or by genetic risk stratification. In multivariate analysis, controlled for genetic risk and year of transplantation, the use of BeEAM conditioning offered no benefit to Mel200 in terms of OS, PFS or risk of relapse/progression. In summary, BeEAM was shown to be a safe and effective conditioning regimen prior to up-front autologous transplant for MM. However, BeEAM conditioning appears to offer no significant advantage when compared to conventional Mel200 conditioning. [Display omitted] DisclosuresSolh: Jazz Pharmaceuticals: Consultancy; BMS: Consultancy; Partner Therapeutics: Research Funding; ADCT Therapeutics: Consultancy, Research Funding. OffLabel Disclosure:Bendamustine for Multiple Myeloma

Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis.

The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p < 0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p < 0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p < 0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes.

Aberrant Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts, Assessed by Next-Generation Flow Cytometry, Is a Negative Predictor for Deep Response Post Autologous Transplantation in Multiple Myeloma; A Prospective Study in 199 Patients.

Simple SummaryAutologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients. However, despite its overall benefit, patients undergo various clinical outcomes post ASCT. Therefore, the identification of biomarkers that could explain, at least partially, this heterogeneity is of utmost clinical significance. The aim of this study was to assess clonal plasma cell contamination of the stem cell grafts of NDMM and evaluate its potency as a predictive/prognostic marker. Our results showed that worse responses to induction therapy correlate with higher levels of graft contamination. Importantly, our data revealed the significantly higher risk of delaying or not achieving complete remission and minimal residual disease (MRD)-negative responses among patients with graft contamination. Graft contamination is emerging as a promising predictive biomarker of clinical relevance that could be used to stratify patients post ASCT.High-dose chemotherapy with autologous stem cell support (ASCT) is the standard of care for eligible newly diagnosed Multiple Myeloma (MM) patients. Stem cell graft contamination by aberrant plasma cells (APCs) has been considered a possible predictive marker of subsequent clinical outcome, but the limited reports to date present unclear conclusions. We prospectively estimated the frequency of graft contamination using highly sensitive next-generation flow cytometry and evaluated its clinical impact in 199 myeloma patients who underwent an ASCT. Contamination (con+) was detected in 79/199 patients at a median level 2 × 10−5. Its presence and levels were correlated with response to induction treatment, with 94%, 71% and 43% achieving CR, VGPR and PR, respectively. Importantly, con+ grafts conferred 2-fold and 2.8-fold higher patient-risk of not achieving or delaying reaching CR (4 vs. 11 months) and MRD negativity (5 vs. 18 months) post ASCT, respectively. Our data also provide evidence of a potentially skewed bone marrow (BM) reconstitution due to unpurged grafts, since con+ derived BM had significantly higher prevalence of memory B cells. These data, together with the absence of significant associations with baseline clinical features, highlight graft contamination as a potential biomarker with independent prognostic value for deeper responses, including MRD negativity. Longer follow-up will reveal if this corresponds to PFS or OS advantage.

Phase 2 study of MGTA-145 + plerixafor for rapid and reliable hematopoietic stem cell (HSC) mobilization for autologous transplant in multiple myeloma.

8023 Background: MGTA-145 (GroβT), a CXCR2 agonist, has shown promising activity for HSC mobilization with plerixafor in pre-clinical models and healthy volunteers. Methods: This phase 2 single center study evaluates HSC mobilization with MGTA-145 + plerixafor and same day apheresis in patients with multiple myeloma. Patients received plerixafor 0.24 mg/kg (0.16 mg/kg if renal dysfunction) SQ, followed 2 hours later by MGTA-145 (0.03 mg/kg) IV over 3-10 minutes and apheresis within 30 minutes. Mobilization was repeated for a second day if day 1 yield was &lt; 6 x 106 CD34+ cells/kg. This interim analysis reports on mobilization in 10 patients (of 25 planned), including safety cohort of first 6 patients completing transplant. Primary endpoint is collection of 2 x 106 CD34+ cells/kg. Results: Median age was 63 years (range: 46-68), 50% were female, 22% had ISS stage 3 &amp; 50% had high-risk FISH. Induction therapy was VRD in 7 and daratumumab + VRD in 3 patients; median induction duration: 4 months (3-6) &amp; median lenalidomide exposure: 6 cycles (4-6), with &gt; VGPR in 70%. Median total stem cell yield (CD34+ cells/kg x 106) was 7.1 (3-16.2), day 1 yield was 5.4 (1.1-16.2) &amp; yield per apheresis session was 4 (1.1-16.2). 100% of patients met the primary endpoint of collecting sufficient HSCs in &lt; 2 days of mobilization + apheresis to proceed to transplant (2 x 106 CD34+ cells/kg). Secondary endpoints of 4 and 6 x 106 CD34+ cells/kg in &lt; 2 days were met in 90% &amp; 80% patients. 30% patients underwent 1 apheresis, while 70% underwent 2 sessions. MGTA-145 was well tolerated. At least 1 adverse event (AE) was seen in 90% of patients, 20% had grade 2 AEs (anemia, hypokalemia) and 20% had grade 3 AEs (worsening of baseline grade 3 anemia; hypocalcemia); all resolved. Acute &amp; transient bone pain was seen in 40% of patients (back-2, hip-1, sternum-1), all grade 1, all on day 1, &amp; resolved without intervention after 6 minutes (3-10). All 6 patients in the safety cohort have completed transplant with melphalan 200 mg/m2. Median of 4.1 (3.4-5.6) x 106 CD34+ cells/kg were infused. All patients have engrafted timely (DiPersio Blood 2009); median time to neutrophil engraftment: 12 days (11-13) &amp; platelet engraftment: 17 days (16-19). Apheresis graft analysis is available in these 6 patients. Grafts with MGTA-145+plerixafor showed high enrichment for CD90+CD45RA- among CD34+ cells, a CD34 subset of long term engrafting HSCs (median: 31% of CD34+ cells, 27-52), higher than seen with G-CSF (6%, Goncalves TCT 2021). 67% of grafts were minimal residual disease negative with next generation flow cytometry. Conclusions: This is the first study to evaluate the novel regimen of MGTA-145 + plerixafor for same day stem cell mobilization &amp; collection in myeloma/hematologic malignancies, with 100% efficacy in interim analysis and the first to demonstrate successful engraftment in patients with cells collected with this GCSF free regimen. Clinical trial information: NCT04552743.

Microenvironment immune reconstitution patterns correlate with outcomes after autologous transplant in multiple myeloma

The immediate postautologous stem cell transplant (ASCT) period in multiple myeloma represents a unique opportunity for long-term disease control because many patients have eradicated most of their disease but also a challenge because it is characterized by the increase of immune subsets detrimental to tumor immunosurveillance. The impact of the tumor immune microenvironment (iTME) in post-ASCT outcomes is not known. In this study, we included 58 patients undergoing upfront ASCT and evaluated their cellular and humoral iTME with cytometry by time of flight (CyTOF) and luminex, respectively, at day +60 to 100 post-ASCT. We identified 2 cellular iTME patterns. Group 1 was enriched in T-cell subsets at the opposite ends of the spectrum of T-cell differentiation compared with the rest of the patients, that is, cells already terminally differentiated (immune senescent or exhausted) and naive T cells. This group had worse hematologic responses post-ASCT, inferior survival, and shorter time to hematologic progression independent of established risk factors. No differences in the humoral iTME were noted between the 2 groups. In addition, no differences in the cellular/humoral iTME were noted according to high-risk fluorescence in situ hybridization status, early or late relapse. Finally, males had higher levels of natural killer cells negative for CD16, a key receptor mediating antibody-dependent cell cytotoxicity, a major mechanism of antitumor efficacy by therapeutic antibodies such as elotuzumab. Our findings suggest that T-cell iTME dysfunction post-ASCT, some of which could be reversible (exhaustion), correlates with worse outcomes. These results could be used to guide rational selection of post-ASCT maintenance/consolidation approaches in these patients.

Serological Response to Vaccination after Autologous Transplantation for Multiple Myeloma Is Associated with Improved Progression-Free and Overall Survival

Revaccination after autologous hematopoietic cell transplantation (AHCT) is recommended in post-HCT survivorship guidelines to restore humoral immunity. Data on seroconversion after AHCT and vaccination in multiple myeloma (MM) patients are limited. We investigated the feasibility and effectiveness of vaccination post-AHCT and analyzed the restoration of humoral immunity and patient prognosis. Anti-pathogen titers were measured within a median of 2 days before and 96 days after AHCT and following revaccination in 139 MM patients who had a first AHCT from 2013 to 2016. Most (84%) patients received at least one dose of any planned vaccines. High-dose melphalan with AHCT restored measurable immunity in 18% of patients. In an additional >60% of patients, seroconversion occurred after vaccination; however, despite vaccination, 20% of patients remained seronegative for most pathogens. Attainment of MM complete response post-AHCT was associated with higher rates of seroconversion which yielded significantly longer progression-free and overall survival. Our study demonstrates the feasibility of post-AHCT vaccination, supporting measurement of post-vaccination titers to determine which patients should be considered for antimicrobial prophylaxis, as seroconversion does not occur in all patients. Titer seroconversion is a potential indicator of the immunological effects of AHCT, with restoration of humoral immunity demonstrating improved survival.

Early Adaptive Natural Killer Cell Expansion Is Associated with Decreased Relapse After Autologous Transplantation for Multiple Myeloma

Adaptive natural killer (NK) cells are long-lived and exhibit properties of immunologic memory against cytomegalovirus (CMV). We previously reported that expansion of adaptive NK cells after CMV reactivation in recipients of allogeneic hematopoietic cell transplantation (HCT) was associated with a lower rate of relapse of acute myelogenous leukemia. In the present study, we examined the impact of adaptive NK cell expansion in a cohort of 110 individuals who underwent autologous HCT (AHCT) for a lymphoid malignancy (lymphoma or multiple myeloma [MM]). In this cohort, higher absolute numbers of adaptive NK cells (>1.58/μL) at day 28 post-AHCT were associated with significantly decreased risk of relapse in patients with MM. No significant association was seen in patients with lymphoma. Further stratification of MM patients by CMV serostatus found a strong protective effect of adaptive NK cells only in CMV-seropositive individuals. These findings suggest that strategies to increase adaptive NK cells after AHCT may be a therapeutic option in patients with MM.

Is Tandem ASCT Needed in MM Patients with High Risk Cytogenetics in the Era of Maintenance Therapy? Results from the Canadian Myeloma Research Group (CMRG) Database

Background: Recent studies evaluating tandem autologous transplantation for multiple myeloma (MM) show conflicting results in terms of efficacy. However subgroup analysis suggests that those with high-risk disease may benefit the most from tandem transplant. We used the CMRG database to compare single versus tandem ASCT for patients with MM with high-risk cytogenetics. Methods: The primary objective was to compare PFS in MM patients with high-risk cytogenetics (p53 deletion, t(4;14), t(14;16)) identified from the CMRG database undergoing front-line single or tandem ASCT from 01/2010 to 06/2019. Secondary objectives compared OS, ORR, and outcomes based on whether post-transplant maintenance was given. OS and PFS rates were calculated from the date of first ASCT using the Kaplan-Meier method. ORR was assessed by Chi-square using best response post ASCT. Results: There were 302 single and 125 tandem transplants, followed by maintenance therapy in 190 (63%) and 96 (77%) respectively. Translocation (4;14) was seen in 209 (49%), t(14:16) in 61 (15.6%) and delP53 in 222 (52%) with more than one abnormality in 65 patients. The most common induction regimen consisted of cyclophosphamide, bortezomib, and steroids, (83%) followed by bortezomib and dexamethasone (8%) and dexamethasone alone (4.7%). Forty-seven patients (11%) required reinduction prior to first ASCT with regimens including RVD (49%), Rd (23%) and others (D/DT/VD-PACE, CyBor-D, KRD, VD, IxaRD, 28%). Maintenance was prescribed to 286 patients with regimens including lenalidomide ± dexamethasone (65%), lenalidomide + proteasome inhibitor ± dexamethasone (22%), proteasome inhibitor ± dexamethasone (11%) and others (2%). Patient characteristics are summarised in table 1. The overall response rate was 93.9% (94.5% for single ASCT and 92% for tandem ASCT). The PFS at 3 years was 41.1% (single) and 45.7% (tandem) with median PFS 26 vs 35 months respectively (p=0.0621). Three year OS was 71.5% (single) and 83.8% (tandem), median OS 83 vs 89 months (p=0.0060). Both PFS and OS were improved with the use of maintenance therapy, regardless of single vs tandem transplant. PFS at 3 years was 52.1% for those receiving maintenance therapy compared to 21.7% for no maintenance (median 42 vs 16 months, p&amp;lt;0.0001). Overall survival was 79.5% with maintenance vs 63.6% without (median 92 vs 60 months, p&amp;lt;0.0001). Figures 1 shows PFS and OS for single or tandem transplant, with or without maintenance therapy. There was no difference in PFS or OS after a single or tandem transplant when maintenance was given. PFS for single or tandem ASCT with maintenance at 3 years was 53.7% and 46.3% respectively (p=0.527). Three year OS rates were 76.7% and 85.6% (p=0.0962). However, PFS was better with tandem compared to single ASCT when no maintenance was given. PFS at 3 years for single transplant with no maintenance was 19.0% (median 13 months) vs 48.9% (median 23.7 months) for tandem without maintenance (p=0.0084), while OS were not statistically different (62.4% vs 74.7%, median 60 months vs not reached, p=0.5271). Conclusions: Tandem ASCT does improve outcomes for MM with high-risk cytogenetics. However, the main benefit was seen in patients who did not receive maintenance therapy. Our data demonstrate the potent anti-myeloma effect of post-ASCT maintenance and raise the question of the optimal role of tandem ASCT in the modern treatment era. Disclosures Duggan: Novartis: Honoraria; Amgen: Consultancy; Celgene: Consultancy; Astra Zeneca: Consultancy; Jannsen: Consultancy. Reece:Janssen, Bristol-Myers Squibb, Amgen, Takeda: Consultancy, Honoraria; Janssen, Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Research Funding; Otsuka: Research Funding. Song:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene,Takeda: Consultancy, Honoraria; Otsuka: Honoraria. Jimenez-Zepeda:Janssen, Celgene, Amgen, Takeda: Honoraria. McCurdy:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Honoraria; GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Louzada:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Mian:Takeda: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Sebag:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding. White:Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria. Stakiw:Lundbeck: Honoraria; Celgene: Honoraria; BMS: Honoraria; Roche: Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria; Novartis: Honoraria. Leblanc:Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Kotb:Takeda: Honoraria; Sanofi: Research Funding; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Karyopharm: Current equity holder in publicly-traded company; Merck: Honoraria, Research Funding. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding.