scholarly journals Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

2021 ◽  
Vol 5 (4) ◽  
pp. 1110-1121 ◽  
Author(s):  
Bob Löwenberg ◽  
Thomas Pabst ◽  
Johan Maertens ◽  
Patrycja Gradowska ◽  
Bart J. Biemond ◽  
...  
Keyword(s):  
Residual Disease ◽  
Complete Response ◽  
Control Group ◽  
Newly Diagnosed ◽  
Clinical Cancer Research ◽  
Free Survival ◽  
Treatment Context ◽  
Middle Aged Adults ◽  
Post Hoc

Abstract Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)–adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.

scholarly journals Case series: MRD negativity assessment using 11C-Acetate PET with 3-weekly daratumumab-based quadruplet induction in newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110303
Author(s):  
Cheong Ngai ◽  
Shaji Kumar ◽  
Garrett Chi-lai Ho ◽  
Sirong Chen ◽  
Chor-sang Chim
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Case Series ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Positron Emission ◽  
Pet Ct ◽  
Subsequent Relapse

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM. However, myeloma outside the BM aspiration site may result in subsequent relapse despite MRD-negativity. Therefore, positron emission tomography-computed tomography (PET-CT) based on F-fluorodeoxyglucose (FDG) is a complementary tool to monitor residual disease in MM. However, FDG may miss myeloma lesions that are not FDG-avid. On the other hand, 11C-Acetate (ACT) has been found to be a more sensitive and specific tracer than FDG in MM. Recently, the addition of daratumumab to bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, lenalidomide, dexamethasone (VRd) backbone has been proven to improve outcomes. Herein, we report three newly-diagnosed MM patients achieving deep responses with imaging CR using ACT PET in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumab-based quadruplet induction regimen.

Inotuzumab ozogamicin (IO) combined with mini-hyper-CVD as salvage therapy for patients (pts) with R/R acute lymphoblastic leukemia (ALL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7025-7025 ◽  
Author(s):  
Rita Assi ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Susan Mary O'Brien ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Intrathecal Chemotherapy ◽  
Free Survival ◽  
Low Intensity ◽  
Transplant Candidates ◽  
Grade 3

7025 Background: Outcome of pts with R/R ALL is poor. IO, a CD22 monoclonal antibody bound to a toxin, calicheamicin, has single-agent activity in R/R ALL with response rate of 80% and median survival of 7.7 months. Adding IO to low-intensity chemotherapy might further improve clinical outcomes. Methods: Pts ≥18 years with R/R ALL were eligible. Chemotherapy was of lower intensity than standard hyper-CVAD and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction (DR), no anthracycline, methotrexate at 75% DR, cytarabine at 0.5 g/m2 x 4 doses). Rituximab (if CD20+ blasts) and intrathecal chemotherapy were given for first 4 courses. IO was given on day 3 of each of the first 4 courses at a dose of 1.8 mg/m2 for cycle 1 then 1.3 mg/m2 for subsequent cycles. After the occurrence of veno-occlusive disease (VOD), IO was modified to 1.3 mg/m2 for cycle 1 followed by 1.0 mg/m2 for subsequent cycles. Results: Sixty pts with a median age of 35 years (range 18-87) were treated. Overall, 47 pts (80%) responded, 32 of them (54%) achieving complete response. The overall minimal residual disease negativity rate among responders was 82%. Grade 3-4 toxicities included prolonged thrombocytopenia (79%), infections during induction and consolidations (52%, and 73% respectively), and hyperbilirubinemia (13%). VOD of any grade occurred in 9 patients (15%). At a median follow-up of 19 months, the median relapse-free survival (RFS) and overall survival (OS) were 9 and 11 months, respectively. The 2-year RFS and OS rates were 33% and 38%. The 2-year OS rates for patients treated in salvage (S)1, S2, and S3 and beyond were 53%, 0%, and 34%, respectively (p = 0.005). When compared to IO monotherapy in a similar pts population, a significant improvement in OS was observed (11 and 6 months, respectively; p = 0.003). Conclusions: The combination of IO with low-intensity mini-hyper-CVD chemotherapy is effective in pts with R/R ALL. Results are encouraging and appear superior to those obtained with IO alone, particularly in pts treated in S1. The risk of VOD should be considered carefully for transplant candidates and pts with previous liver damage. Lower dose of weekly schedules of IO are being explored Clinical trial information: NCT01371630.

scholarly journals Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial

Blood ◽  
2020 ◽  
Vol 136 (8) ◽  
pp. 936-945 ◽  
Author(s):  
Peter M. Voorhees ◽  
Jonathan L. Kaufman ◽  
Jacob Laubach ◽  
Douglas W. Sborov ◽  
Brandi Reeves ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Depth Of Response ◽  
Grade 3 ◽  
Intent To Treat

Abstract Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patients (N = 207) were randomized 1:1 to D-RVd or RVd induction (4 cycles), ASCT, D-RVd or RVd consolidation (2 cycles), and lenalidomide or lenalidomide plus D maintenance (26 cycles). The primary end point, stringent complete response (sCR) rate by the end of post-ASCT consolidation, favored D-RVd vs RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval, 0.87-2.82; 1-sided P = .068) and met the prespecified 1-sided α of 0.10. With longer follow-up (median, 22.1 months), responses deepened; sCR rates improved for D-RVd vs RVd (62.6% vs 45.4%; P = .0177), as did minimal residual disease (MRD) negativity (10−5 threshold) rates in the intent-to-treat population (51.0% vs 20.4%; P < .0001). Four patients (3.8%) in the D-RVd group and 7 patients (6.8%) in the RVd group progressed; respective 24-month progression-free survival rates were 95.8% and 89.8%. Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but grade 3/4 infection rates were similar. Median CD34+ cell yield was 8.2 × 106/kg for D-RVd and 9.4 × 106/kg for RVd, although plerixafor use was more common with D-RVd. Median times to neutrophil and platelet engraftment were comparable. Daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. This trial was registered at www.clinicaltrials.gov as #NCT02874742.

scholarly journals Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN

2021 ◽  
Vol 5 (4) ◽  
pp. 1092-1096
Author(s):  
Peter M. Voorhees ◽  
Cesar Rodriguez ◽  
Brandi Reeves ◽  
Nitya Nathwani ◽  
Luciano J. Costa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Survival Rates ◽  
Final Analysis ◽  
Complete Response ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Best Response

Abstract The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.8 months) encompassing daratumumab plus lenalidomide (D-R) maintenance therapy. Patients in the safety run-in cohort (N = 16) received 4 induction cycles (D-RVd), high-dose melphalan supported by autologous stem cell transplant, 2 consolidation cycles (D-RVd), and 24 months of maintenance (D-R). By the end of consolidation, all patients had responded, with a best response of sCR in 9 (56.3%) patients; 8 (50.0%) patients were minimal residual disease (MRD) negative (10‒5 threshold). After maintenance, 15 (93.8%) patients had achieved a best response of sCR, and 13 (81.3%) patients were MRD (10‒5) negative. Estimated 36-month progression-free and overall survival rates were 78.1% and 93.8%, respectively. One death from progressive disease occurred in the patient who did not achieve sCR. Observed safety profiles were consistent with daratumumab and RVd. With >3 years of median follow-up, D-RVd achieved durable responses that deepened with D-R maintenance. This study was registered at www.clinicaltrials.gov as #NCT02874742.

Favorable Impact of Post-ASCT Consolidative Immunotherapy with RITUXIMAB, rINF-a2b and rIL2 on Overall Survival and Progression-Free Survival in Advanced Stage or Relapsed/Refractory Follicular Lymphoma: Results of a Phase II Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3066-3066 ◽  
Author(s):  
Jean-Richard Eveillard ◽  
Jean-Christophe Ianotto ◽  
Adrian Tempescul ◽  
Gaelle Guillerm ◽  
Florence Dalbiès ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Control Group ◽  
Study Group ◽  
Subcutaneous Injections ◽  
Free Survival ◽  
Minimal Residual

Abstract Abstract 3066 Introduction: Advanced stage III/IV or relapsed/refractory follicular lymphoma (FL) can hardly be cured with conventional chemotherapy and patients, even after autologous stem cell transplantation (ASCT), experience innumerable relapse events occurring at decreasing progression-free intervals. Important progress was made since the introduction of RITUXIMAB as part of frontline chemoimmunotherapy or as maintenance after frontline treatment with or without ASCT. But, whatever the policy applied, no plateau is observed regarding overall survival (OS) and progression-free survival (PFS). Disease relapse, even in patients with documented complete remission (CR), is thought to be induced both by resistant minimal residual tumor cells and the lack of immunocompetent mechanisms to contain or eliminate them. Thus, it has been postulated that post-ASCT consolidative immunotherapy might eradicate minimal residual disease, based on antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism, and have a favorable impact on relapse rate and even OS. This view has led to a considerable interest in immunotherapy as a promising therapeutic line to restore and enhance the impaired anti-tumor immune surveillance in the context of post-ASCT low tumor burden. Purpose: We conducted a phase II study to compare OS and PFS between patients with advanced or relapsed/refractory FL receiving consolidative immunotherapy combining recombinant interleukine-2 (rIL-2), recombinant interferon- α-2b (rINF- α-2b) and RITUXIMAB after ASCT, with the aim of controlling minimal residual disease, and other counterparts with FL receiving no further treatment after ASCT. Patients and Methods: From August, 1995, to October, 2009, 139 patients with FL were autografted in complete remission ≥1 or partial remission. Of these patients, 66 were considered eligible for immunotherapy. On adequate post-ASCT hematologic reconstitution, they received 4 weekly IV injections of RITUXIMAB administered on an outpatient fashion. This was followed by a home-based program of subcutaneous injections of rIL2 (6 million UI × 3 / week in 1st cycle; 9 million × 3 / week in 2d) and rINF- α-2b (1.5 million UI × 3 / week in 1st cycle; 3 million × 3 / week in 2d) administered over two 7-week cycles. These two cycles were separated by a two-week free interval. The other 73 patients did not receive any additional treatment after ASCT and served as controls. Results: The two groups were comparable regarding demographic characteristics, disease profile and treatment course, except that the control group had significantly less transformed FL (p =0.0156) and a higher mean treatment line number (p =0.018). Median OS and PFS were not reached in either the study group or the control group. OS, initially not different between the 2 groups (p =0.21), was found significantly higher in the study group after a cut-off follow-up time point of 86.6 months (p =0.017). A significantly higher PFS was also noted in favor of the study group over the control group (p =0.0131). With a median follow-up of 60 months (10 to 136) in the study group and of 82 months (0.7 to 174) in the control group, survival rate was 90.9% and 71.2%, respectively (p= 0.0034) and the overall relapse rate was 19.7% (13 patients) and 41.1% (30 patients), respectively (p= 0.0064). Adverse events were generally mild, consisting essentially of fever and chills with the rIL-2 and rINF- α-2b subcutaneous injections (rapidly controlled with PARACETAMOL), fatigue, grade 2 abnormal liver function tests in one third of patients and grade 2 or 3 cytopenias (anemia or neutropenia) in 40% of patients. Conclusion: These results confirm that post-ASCT immunotherapy with rIL2, rINF- α-2b and RITUXIMAB has a statistically significant impact on OS and PFS. In view of its tolerability, it appears to be quite feasible and safe and might be seen as a promising line of treatment designed for eradicating post-ASCT minimal residual disease and worth being tested within the frame of a randomized trial for validation as an essential step in the treatment algorithm of FL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma

Blood ◽  
2019 ◽  
Vol 133 (18) ◽  
pp. 1953-1963 ◽  
Author(s):  
Thierry Facon ◽  
Jae Hoon Lee ◽  
Philippe Moreau ◽  
Ruben Niesvizky ◽  
Meletios Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Intention To Treat ◽  
Significant Difference ◽  
Grade 3

Abstract The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease–negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials.gov as #NCT01818752.

Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
The Elderly ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Common Sign ◽  
Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Philippe Moreau ◽  
Pieter Sonneveld ◽  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Second Primary ◽  
Cell Transplant ◽  
Open Label ◽  
Depth Of Response

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.

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