Impact of post-ASCT maintenance therapy on outcomes in patients with newly diagnosed multiple myeloma in Connect MM

Abstract

Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Clinical trials show progression-free survival (PFS) benefits, with some studies (Cancer and Leukemia Group [CALGB] trial and meta-analysis) also showing overall survival (OS) benefits, but applicability to real-world clinical settings is unclear. Using data from Connect MM, the largest US-based observational registry of NDMM patients, we analyzed effects of maintenance therapy on long-term outcomes in 1450 treated patients enrolled from 2009 to 2011. Patients who received induction therapy and ASCT (n = 432) were analyzed from 100 days post-ASCT (data cut 7 January 2016): 267 received maintenance (80% lenalidomide-based [of whom 88% received lenalidomide monotherapy]); 165 did not. Lenalidomide maintenance improved median PFS and 3-year PFS rate vs no maintenance (50.3 vs 30.8 months [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.46-0.82; P < .001] and 56% vs 42%, respectively). Improvements in median OS and 3-year OS rate were associated with lenalidomide maintenance vs no maintenance (not reached in either group [HR, 0.54; 95% CI, 0.36-0.83; P = .005] and 85% vs 70%, respectively). Five hematologic serious adverse events were reported with lenalidomide maintenance (pancytopenia [n = 2], febrile neutropenia, anemia, and thrombocytopenia [n = 1 each]) and 1 with no maintenance (thrombocytopenia). Second primary malignancies occurred at rates of 1.38 and 2.19 events per patient-year in lenalidomide maintenance and no maintenance groups, respectively. Survival benefits associated with lenalidomide maintenance previously demonstrated in clinical trials were observed in this community-based Connect MM Registry.

Conflict of interest statement

Conflict-of-interest disclosure: S.J. provided consulting services to Celgene, Bristol-Myers Squibb, Novartis, and Merck, and was on speakers’ bureaus for MMRF and Medicom. R.A. received research funding from Celgene, Takeda, and Prothena. B.G.M.D. provided consulting services to Takeda and Janssen. M.N. provided consultancy services to Celgene, and was on speakers’ bureaus for Celgene and Janssen. H.R.T. provided consulting services to Celgene and was on speakers’ bureaus for Janssen, Takeda, and Pharmacyclics LLC, an AbbVie Company. C.J.G. provided consulting services to Celgene, Takeda, and Janssen; received research funding from Celgene; and received reimbursement for travel expenses from Celgene and Janssen. K.T. provided consulting services to Celgene; was on a speakers’ bureau for Myriad Genetics; and received reimbursement for travel expenses from Dava Oncology. J.W.H. provided consulting services to Celgene. L.W. provided consulting services to EveryFit, Gilead, and Janssen. A.A., E.D.F., S.S., A.K., and M.S. are employed by, and have stock in, Celgene. R.M.R. provided consulting services to Amgen, Boehringer Ingelheim, Celgene, EMD Serono, Sandoz, and Takeda, and has stock in McKesson.

© 2018 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Study design. Patients in cohort 1 who received induction therapy and ASCT were included and analyzed by first-line post-ASCT maintenance therapy. The exploratory analysis was performed on groups with adequate sample sizes (lenalidomide maintenance therapy and no maintenance therapy). SCT, stem cell transplantation.

Figure 2.

Survival for patients treated with lenalidomide vs no maintenance therapy. Patients receiving post-ASCT lenalidomide maintenance therapy had improved (A) PFS (P < .001) and (B) OS (P = .005) compared with those who did not receive maintenance therapy. Analysis was adjusted for covariates of ECOG performance status, serum creatinine level, treatment with a novel agent, treatment with lenalidomide, treatment with bortezomib, and triplet treatment during first-line induction therapy.

Figure 3.

Exploratory survival subgroup analysis for lenalidomide vs no maintenance therapy. Improvements in (A) PFS and (B) OS observed with lenalidomide maintenance therapy were generally similar across all subgroups.

Figure 4.

PFS (unadjusted) and OS (unadjusted) by IMWG risk criteria. (A) PFS and (B) OS were similar among IMWG high- and standard-risk patients receiving lenalidomide (Len) maintenance therapy, but poorest in high-risk patients with no maintenance therapy.

Figure 5.

Second PFS for lenalidomide vs no maintenance therapy. Median second PFS was similar between the 2 groups. Only patients who had first progression were considered for this analysis.