scholarly journals Outcome of Patients with Hodgkin Lymphoma Treated with Brentuximab Vedotin for Relapse after Autologous Stem Cell Transplant: A Retrospective Analysis of the LWP-EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4018-4018
Author(s):  
Nikesh Dhiraj Chavda ◽  
Stephen Robinson ◽  
Ariane Boumendil ◽  
Irma Khvedelidze ◽  
Hervé Finel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Travel Grant

Around half of patients with Hodgkin Lymphoma (HL) who progress or relapse through first line therapy can be cured with salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, this leaves approximately 50% of patients that will relapse after ASCT. The pivotal phase II SG035-00303 trial demonstrated that these patients can be successfully treated with Brentuximab Vedotin (BV), and a proportion of them can be long term free of disease without any further intervention. The objective of the current study was to investigate whether these findings were borne out in the real world via interrogation of the EBMT registry. We retrospectively analysed data for 101 patients with HL who had BV as their first treatment for relapse after ASCT from 2012 to 2019. The median age at ASCT was 34 years (range: 19-65), 60% being male and with 62% being in complete response (CR) at the time of ASCT. Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) was the most common conditioning regimen, having been employed in 72% of the cases. The median time from ASCT to relapse was 10.1 months (interquartile range (IQR): 6.1-25.1). The median time on BV was 3.4 months (IQR: 2.1-5.24). BV treatment resulted in a best overall response rate (ORR) of 59% with a CR rate of 37%. At last follow-up only 2 patients remain on treatment with BV. The main reason for discontinuation of BV was progression which occurred in 37% of the patients. In 32 cases (33%) the treatment was stopped electively to proceed to a second transplant, and overall nearly a quarter (22%) completed the full treatment course. Only 5% of patients stopped due to toxicity (peripheral neuropathy 2 and neutropenia, infusion reaction and other, 1 each). Further therapy was given after BV in over half of evaluable patients (58%), with check point inhibitors (CPIs) being the most common agents used (24% of these). Nearly two thirds (64/101) of the patients received a second transplant, which were nearly all allogeneic stem cell transplant (alloSCT, 59/64), and most of these (49/59) with reduced intensity conditioning (RIC). 26% of the alloSCT recipients experienced grade II-IV acute graft versus host disease (GvHD) and 25% developed chronic GvHD. At last follow up, 62% of all patients were alive with a median follow-up of 25 months after starting BV. Of these, 27 had received a second transplant, who were mostly in CR at last follow up (26/27) and a further 22 had relapsed. There were 11 patients of the 63 still alive who continued to be responding to BV without further therapy with a median duration of response of 30 months. In conclusion BV use for relapse after ASCT was well tolerated generally, with only a minority of patients stopping treatment due to toxicity. However, although almost two thirds of the patients achieved a response, further treatment was often needed after BV, notably with CPIs and most patients were consolidated with a RIC alloSCT. These results confirm that only a minority of patients can achieve a durable remission with BV alone. Disclosures Brice: Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria. Stamatoullas:Celgene: Honoraria; Takeda: Consultancy. Robak:Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta: Research Funding; Morphosys AG: Research Funding. Wahlin:Roche and Gilead: Consultancy.

FDG-PET Adapted Sequential Therapy With Brentuximab Vedotin and Augmented ICE Followed By Autologous Stem Cell Transplant For Relapsed and Refractory Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2099-2099 ◽  
Author(s):  
Alison Moskowitz ◽  
Heiko Schoder ◽  
John F. Gerecitano ◽  
Paul Hamlin ◽  
Steven M. Horwitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Salvage Therapy ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Genetics Research ◽  
Grade 3

Abstract Background Pre-transplant FDG-PET (PET) normalization is the strongest predictor of outcome following autologous stem cell transplant (ASCT) for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) (Moskowitz, AJ. Blood. 2010 Dec 2;116(23):4934-7). Due to its high efficacy in ASCT failures, we aimed to determine whether brentuximab vedotin (BV) can replace ICE (ifosfamide, carboplatin, etoposide) salvage therapy, increase rate of PET normalization, and enhance referral to ASCT for patients (pts) who fail front-line HL therapy. Here we present our phase II study evaluating a novel salvage strategy for rel/ref HL, an intent-to-treat study of PET-adapted sequential therapy with BV and augmented ICE (augICE) prior to ASCT. Methods Patients with rel/ref HL who have failed 1 prior regimen are enrolling on this phase II clinical trial. Patients receive weekly brentuximab vedotin (BV) administered at 1.2mg/Kg IV weekly for 3 weeks on and 1 week off for 2 cycles, followed by PET. Patients who achieve normalization of PET (Deauville 2 or less) proceed to ASCT. Patients with PET scores of Deauville 3 or higher receive 2 cycles of augICE prior to consideration for ASCT. Results 41 of planned 46 patients have enrolled; 34 pts completed salvage therapy, of whom 33 proceeded to ASCT. 28 pts are at least 90 days post-ASCT and represent the focus of this report. These 28 pts include 20 (71%) males, 21 (75%) pts with primary refractory or relapse within 1 year of initial treatment, 11 (39%) with B symptoms at enrollment and 11 (39%) with extranodal disease. Median number CD34+ cells/kg collected were 7.44x 10^6 (2.96 - 31.43x10^6). Disease status prior to ASCT was CR (Deauville 2) for 27 pts and PR (Deauville 3) for 1 pt. Salvage therapy for pts in CR prior to ASCT include BV alone (9), BV followed by augICE (16), and BV followed by augICE (with Deauville 4 response) followed by involved field radiation to achieve CR (2). The 1 patient in PR prior to ASCT received BV followed by augICE. Conditioning regimens included BEAM (9), CBV( 9), and high dose chemoradiotherapy (10). Early (within 90 days) transplant-related toxicities include grade 2 pneumonitis (3pts) and grade 3 acute kidney injury (1pt); late toxicities include grade 3 esophageal stenosis (1pt), grade 3 acute kidney injury (1pt), and 1 death (7 months post ASCT) due to progressive multifocal leukoencephalopathy. After a median follow-up of 9.5 months post-ASCT (range 3.3-15.6 months), 2 of 28 pts have progressed (at 2.7 and 4.3 months post ASCT respectively). One achieved a second CR with BV and proceeded to allogeneic stem cell transplant (alloSCT); the second achieved near CR following GND (gemcitabine, vinorelbine, Doxil) and proceeded to alloSCT. Conclusion PET-adapted sequential salvage therapy with BV followed by augICE produces high CR rates, adequate stem cell collection, and facilitates referral to ASCT for virtually all pts. Updated results will be presented at the meeting. Disclosures: Moskowitz: Seattle Genetics: Research Funding. Off Label Use: Brentuximab vedotin is approved for treatment of Hodgkin lymphoma following failure of 2 multi-agent regimens or autologous stem cell transplant. This study is evaluating the use of brentuximab vedotin in the pre-transplant setting for Hodgkin lymphoma. Schoder:Seattle Genetics: Research Funding. Hamlin:Seattle Genetics : Consultancy, Honoraria. Horwitz:Millennium: Consultancy, Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding. Moskowitz:Seattle Genetics: Research Funding.

The Aethera Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 673-673 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Auayporn Nadamanee ◽  
Tamas Masszi ◽  
Edward Agura ◽  
Jerzy Holowiecki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Salvage Therapy ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Frontline Therapy

Abstract Background For the past 20 years, high-dose therapy plus autologous stem cell transplant (ASCT) has been the standard of care for patients (pts) with chemosensitive relapsed/refractory Hodgkin lymphoma (HL), providing a cure for approximately 50% of pts (Sureda 2005). Despite optimization of salvage chemotherapy, supportive care, and pt selection, improvements in outcomes post-ASCT have plateaued, likely due to disease progression (PD) in pts with pre-salvage therapy risk factors. The majority of pts with multiple risk factors will progress post-ASCT and novel therapy is urgently needed. Brentuximab vedotin (ADCETRIS®) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE), and has an objective response rate of 75% in relapsed or refractory HL. The AETHERA trial was initiated to evaluate whether early treatment with brentuximab vedotin post-ASCT can prevent progression in pts with HL (ClinicalTrials.gov #NCT01100502). Methods The AETHERA trial is a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Pts were enrolled in 1 of 3 high-risk categories: refractory to frontline therapy: 196 pts (60%), relapse <12 months after frontline therapy: 107 pts (33%), and relapse ≥12 months after frontline therapy with extranodal disease: 26 pts (8%). Pts were required to have obtained a CR, partial remission (PR), or stable disease (SD) to salvage therapy prior to ASCT. After ASCT, pts received brentuximab vedotin 1.8 mg/kg q3wk and best supportive care (BSC) or placebo and BSC for up to 16 cycles (approximately 12 months). Pts with PD were to discontinue study therapy and could request unblinding; these pts may have received subsequent brentuximab vedotin on another clinical trial or on-label in some regions. The primary endpoint is PFS per an independent review facility (IRF); additional endpoints include overall survival (OS) and safety/tolerability. Results A total of 329 pts were randomized at 78 sites in the United States and Europe. Of the 329 enrolled pts, 327 received study treatment. The median age was 32 years (range, 18–76) and 53% were male. The median number of prior systemic therapies (frontline and salvage) was 2 (range, 2–8); 47% of pts received more than 2 prior systemic therapies. Response to salvage therapy pre-ASCT was CR: 137 pts (42%), PR: 112 pts (34%), and stable disease (SD): 80 pts (24%). Prior to pre-ASCT salvage therapy, 106 pts (32%) had extranodal involvement and 87 pts (26%) had B symptoms. Prior to ASCT, 110 pts (33%) were PET negative, 116 pts (35%) were PET-positive and PET status was unknown for 103 pts (31%). Overall, 78% of pts had multiple risk factors for progression. All pts had completed or discontinued study treatment as of August 2013. The median number of treatment cycles was 15, and 159 pts (49%) received 16 cycles. Reasons for treatment discontinuation were: PD: 93 pts (28%), adverse event (AE): 61 pts (19%), patient decision: 15 pts (5%), and investigator decision: 1 pt (<1%). At the time of this analysis (June 2014), the median follow-up time from randomization was 24.4 mos (range, 0–43 mos). For the pooled study population at 24 mos, the Kaplan Meier estimates were 54% (95% CI: 47%, 60%) for PFS and 88% (95% CI: 84%, 91%) for OS. Of the 50 deaths, 8 occurred prior to PD. AEs of any grade in >15% of pts were peripheral sensory neuropathy (36%), upper respiratory tract infection (25%), neutropenia (24%), fatigue (21%), cough (19%), and pyrexia (17%). Grade 3 or higher AEs in ≥10 pts were neutropenia (20%), peripheral sensory neuropathy (6%), thrombocytopenia (3%), and peripheral motor neuropathy (3%). As assessed by a Standardised MedDRA Query, 144 pts (44%) had treatment-emergent events of peripheral neuropathy (PN). Grade 3 PN was reported for 23 pts (7%) and was mostly sensory; no Grade 4 events were observed. Resolution or at least 1 grade of improvement in PN has occurred in 80% of pts with neuropathy events; the median time to resolution or improvement was 11.7 weeks (range, 0.1–128.0 weeks). Conclusions Based on analysis of blinded pooled efficacy data, the estimated 2-year PFS rate was 54% and the estimated 2 year OS rate was 88%. The most common reason for treatment discontinuation was disease progression. The primary analysis for the study will be performed in September 2014 and unblinded efficacy and safety data will be publicly presented for the first time at the conference. Figure 1 Figure 1. Disclosures Moskowitz: Genentech: Research Funding; Merck: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding. Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. Nadamanee:Gilead: Consultancy; Celgene: Consultancy; Spectrum: Research Funding; Seattle Genetics, Inc.: Research Funding. Masszi:Seattle Genetics, Inc.: Research Funding. Agura:Seattle Genetics, Inc.: Research Funding. Holowiecki:Seattle Genetics, Inc.: Research Funding. Abidi:Seattle Genetics, Inc.: Research Funding, Speakers Bureau. Chen:Seattle Genetics, Inc.: Research Funding. Stiff:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Gianni:Seattle Genetics, Inc.: Research Funding. Carella:Seattle Genetics, Inc.: Research Funding. Osmanov:Seattle Genetics, Inc.: Research Funding. Bachanova:Seattle Genetics, Inc.: Consultancy, Research Funding. Sweetenham:Seattle Genetics, Inc.: Honoraria, Research Funding, Speakers Bureau. Sureda:Takeda Pharmaceuticals International Co.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics, Inc.: Research Funding. Huebner:Takeda Pharmaceuticals International Co.: Employment, Research Funding. Larsen:Seattle Genetics, Inc.: Employment, Equity Ownership. Hunder:Seattle Genetics, Inc.: Employment, Equity Ownership. Walewski:Seattle Genetics, Inc.: Research Funding; Takeda Poland: Consultancy, Travel expenses, Travel expenses Other.

Prediction of Progression-Free Survival with Brentuximab Vedotin Therapy for Relapsed Hodgkin Lymphoma: A Retrospective Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3086-3086
Author(s):  
Anna Houk ◽  
Ajay K. Gopal ◽  
Edward N. Libby ◽  
Andrei R. Shustov ◽  
Damian J. Green ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Confidence Intervals ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Free Survival

Abstract Introduction: The role of brentuximab vedotin (BV) in Hodgkin Lymphoma (HL) is expanding, but factors predicting progression-free survival (PFS) after BV therapy are poorly defined. Age, tumor bulk, presence of extranodal disease, neutrophil:lymphocyte ratio (ANC/ALC), and lymphocyte:monocyte ratio (ALC/AMC) predict outcome in HL patients (pts) treated with chemotherapy, but their impact on PFS after BV has not been well-studied. Also, among pts with relapsed/refractory HL (rel/ref HL) who progress after BV, efficacy of additional chemotherapy is undefined. To inform patient selection and future clinical trial design with BV, we undertook a retrospective study to identify factors predicting PFS with BV therapy in rel/ref HL, and explore chemotherapy efficacy as salvage after BV failure. Methods: Pts receiving BV since 2009 were identified through pharmacy and research records and studied with IRB approval. Those with rel/ref HL receiving BV before or after transplant without intervening therapy were excluded. Age ≥40 at time, sex, pre-BV PET findings (SUV max, extranodal [EN] involvement, bulk > 5cm), prior therapy (# lines of therapy> median; prior transplant, platinum-containing, radiotherapy), and lab findings (AMC/ALC³4.3, ALC/AMC ratio³1) at time of start of BV were examined for an impact on PFS and OS via log-rank testing of Kaplan-meier projections(JMP 11.0 software). PFS was defined as time from first BV dose to radiographic or clinical progression, initiation of post-BV salvage, or death from any cause. OS was measured from date of first BV dose to death from any cause. Efficacy of salvage therapy for those failing BV was recorded. Results: Of 90 patient receiving BV, 43 met above criteria. Median age was 34 yrs (range 17-80), median # of pre-BV therapies was 3 (range 1-7). 31 (73%) had failed autologous transplant, 10 (23%) had undergone allogeneic transplant, and 20 (46%) received radiotherapy prior to BV. Pre-BV PET staging data was available in 26 pts; post-BV PET was not analyzed in this dataset as response criteria were nonstandardized. BV was administered for a median 6 cycles (range 2-20). Median PFS after BV was 6 mo. (Figure 1) with 4 pts having PFS >4 yrs. At 31 mo. median follow-up, 71% of pts were alive with no plateau in the survival curve. On univariate analysis, age 40 or older at time of BV predicted inferior PFS (p=.03) and inferior OS though 95% confidence intervals were wide (OS by age: Figure 2, p=.02). HR for death for pts age 40 or older was 4 (98% CI .03-2.3, p=.05). No other factor predicted PFS or OS. Among 29 pts who failed BV, OS was 3.4 yrs. 40 chemotherapy regimens were given with 11 responses. Five of 11 pts responded to bendamustine, but median time to progression was 4 mo. Two of 4 responded to gemcitabine as did 3/8 receiving platinum chemotherapy. Conclusions: In this cohort of rel/ref HL pts treated with BV, PFS was 6 mo. overall and inferior among pts 40 yrs or older. OS was also worse in this group, although confidence intervals were wide in both univariate analyses. We confirm and expand upon prior data showing features predicting outcomes in HL after chemotherapy do not clearly apply after BV; and that most pts progress <1 year after single-agent BV with a few durable remissions. Salvage chemotherapy after BV has transient efficacy. Larger studies defining clinical, biologic, and PET-based markers of outcome after BV are needed. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Off Label Use: Brentuximab is approved in HL after failure of autologous stem cell transplant; in this series, some patients received Brentuximab before or when ineligible for an autologous stem cell transplant.. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Gilead: Research Funding; Spectrum: Research Funding; Teva: Research Funding. Shustov:Seattle Genetics, Inc.: Research Funding.

Patterns of Relapse Among Myeloma Patients Post-Autologous Stem Cell Transplant

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4524-4524
Author(s):  
Prashanth Kumar ◽  
Nisha Joseph ◽  
Dhwani Almaula ◽  
Lawrence H Boise ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Biochemical Relapse ◽  
Entire Cohort ◽  
Symptomatic Relapse

Abstract Introduction: In younger patients that are transplant-eligible, autologous stem cell transplant (ASCT) prolongs overall survival based on several prospective randomized control trials. Nevertheless, ASCT is not a curative approach and majority of the patient's relapse, requiring further salvage therapeutic options. However, in the face of an ongoing paradigm shift in myeloma therapeutics, there is a significant knowledge gap regarding how patients relapse following ASCT. We analyzed the patterns of relapse among myeloma patients after ASCT. Methodology: We have evaluated a total of 975 patients that underwent ASCT during the period January 2008 through June 2014 from our myeloma database. 273 patients had documented evidence of first relapse post-ASCT on the laboratory parameters, radiologic or pathologic findings based on IMWG criteria for relapse. We categorized the relapses as biochemical vs symptomatic, and described their frequencies and characteristics. Median time of follow up from diagnosis is 68 months and from ASCT is 54 months. We used IBM SPSS version 23.0 to generate the survival statistics. Results: Median time from ASCT to relapse is 20 months. A total of 182 (66.7%) patients (105M, 77F) experienced biochemical relapse, while 91 (33.3%) patients (50M, 41F) had symptomatic relapse. More IgA patients (30.8% vs 23.1%, p=0.06) relapsed as symptomatic myeloma. While characterizing relapses, we did not find any differences in symptomatic relapses by the risk group [high risk (31.3%) vs standard risk (31.9%), p=0.193, ISS stage I (29.3%) vs II (32.9%) vs III (32.8%), p=0.807] or by maintenance [yes (30.7%) vs no (38.1%), p=0.211]. Among the patients that had a symptomatic relapse, presence of new bone lesions (52%) and anemia (42%) are the most common forms of relapse seen. Only 4% presented as hypercalcemia and 1% presented as renal failure illustrating the benefits of closer follow up. Overall survival is similar among patients that relapsed as biochemical or symptomatic relapse (log rank, p=0.105). More importantly, impressive median OS of 145 months from the ASCT among this entire cohort (at median follow up 54 months, figure 1). Conclusions: Two-thirds of the patients relapse as a biochemical relapse post-ASCT. The patterns of biochemical vs symptomatic relapses were similar among patients by maintenance, by risk status and also by the ISS stage. The significant improvement in OS among the entire cohort emphasizes the power of the new therapeutic salvage strategies aimed at gaining the survival advantage even among this selected group of patients undergoing early relapses. Disclosures Kaufman: Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Incyte: Consultancy; Pharmacyclics: Consultancy. Lonial:Novartis: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Onyx: Consultancy; Merck: Consultancy; Janssen: Consultancy; BMS: Consultancy; BMS: Consultancy; Millenium: Consultancy; Celgene: Consultancy. Nooka:Spectrum, Novartis, Onyx pharmaceuticals: Consultancy.

scholarly journals Efficacy of Daratumumab Containing Regimens Post Lenalidomide Maintenance in Transplant Eligible Patients: Real-World Experience from the Canadian Myeloma Research Group Database

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Hira S Mian ◽  
Christine Eisfeld ◽  
Christopher P. Venner ◽  
Victor Jimenez-Zepeda ◽  
Cyrus Khandanpour ◽  
...  
Keyword(s):  
Stem Cell ◽  
Real World ◽  
Research Group ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
P Value ◽  
Cell Transplant ◽  
Second Line

Introduction Lenalidomide maintenance following autologous stem cell transplant (ASCT) remains a standard of care among transplant eligible patients with newly diagnosed multiple myeloma (NDMM). Many previous clinical trials done in patients following one prior line of therapy either excluded patients progressing on lenalidomide or included a very small proportion of these patients. Given the paucity of data in this setting, the optimal management of patients progressing on lenalidomide maintenance remains unknown. Daratumumab-containing triplet regimens have recently been introduced for these patients, typically in combination with pomalidomide (DPd), lenalidomide (DRd), or bortezomib (DVd). To our knowledge, there is no prospective data to allow comparison of the efficacy of these three regimens in patients progressing on lenalidomide maintenance, which is an increasingly common clinical scenario. Understanding the comparative efficacy, tolerability and toxicity of these regimens in patients progressing on lenalidomide maintenance in the 'real-world' is needed in order to help clinicians make appropriate decisions and guide future studies. Methods The Canadian Myeloma Research Group Database (formerly known as the Myeloma Canada Research Network Database, MCRN-DB) is a prospectively maintained disease specific database with over 7000 patients enrolled from 14 academic sites across Canada with legacy data collected from 2007. The Munster Myeloma database collects myeloma specific information in a German academic center and currently contains data from 800 patients collected from 2005. All consecutive patients treated with daratumumab based regimens in second line following relapse on lenalidomide maintenance were included in the analysis from the two databases analyzed up to 30/06/2020. Results A total of 1380 NDMM patients on lenalidomide maintenance post autologous stem cell transplant were identified in the two databases. From them, 73 patients were included in this analysis as they were treated with daratumumab containing regimen in second line. Specifically, 18 (24.7%) of these patients were treated with DPd, 32 (43.8%) patients with DRd, and 23 (31.5%) patients with DVd. The baseline characteristics, maintenance details, post-maintenance response rates and toxicity for each regimen are shown in Table 1. The median follow-up for the cohort from the time of daratumumab initiation was 8.3 months (range 0.4 - 40.0). Although, a higher proportion of patients in the DPd arm obtained a CR/VGPR compared to DRd or DVd, it did not reach statistical significance (p-value 0.06). The median PFS of the entire cohort was 16.96 months (95% CI 11.47-23.44). The median PFS of the individual regimens was as follows: DPd 17.65 months, DRd not reached and DVd 11.47 months as demonstrated in Figure 1 (p-value =0.46). Conclusion In summary, our results show that daratumumab-based regimens are effective among patients progressing on lenalidomide maintenance in the real world. Despite the small sample size, the results presented here are in line with recent sub-analyses of phase III studies examining the common daratumumab-based regimens used in this setting (CASTOR with median PFS of DVd between 7.8 months in all lenalidomide refractory patients and 27 months in all patients in first relapse; MM014 with median PFS of DPd after lenalidomide refractoriness of 21.8 months). The efficacy of DRd, in which daratumumab is added to an increased dose of lenalidomide, is notable and warrants further evaluation to identify which patients are most likely to benefit. Additional studies with longer follow-up are required to assess the optimal daratumumab-based regimen to be used in this growing population of patients relapsing after lenalidomide maintenance. Disclosures Mian: Janssen: Consultancy, Honoraria; Celgene: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Jimenez-Zepeda:Janssen, Celgene, Amgen, Takeda: Honoraria. McCurdy:Sanofi: Honoraria; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Sebag:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding. Song:Celgene: Research Funding; Celgene, Janssen, Amgen, Takeda: Honoraria. Leblanc:Celgene: Research Funding; Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. White:Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Stakiw:Roche: Research Funding; Celgene: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; BMS: Honoraria. Louzada:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kotb:Karyopharm: Current equity holder in publicly-traded company; Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Merck: Honoraria, Research Funding; Sanofi: Research Funding. Reece:Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Amgen: Consultancy, Honoraria; Millenium: Research Funding; BMS: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding.

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