Bortezomib-based maintenance therapy provided no added outcome benefit compared with lenalidomide alone in patients with high-risk multiple myeloma (MM) undergoing autologous hematopoietic cell transplant (AHCT), according to a study published in Cancer.
“Physicians are good at identifying the high-risk patients where perhaps lenalidomide maintenance alone is suboptimal,” said corresponding author Anita D’Souza, MD, MS, of the Medical College of Wisconsin in Milwaukee. “However, based on our analysis, bortezomib or bortezomib-based maintenance did not improve outcomes for this group of patients. Thus, in clinical practice, high-risk patients should strongly be considered for clinical trials testing novel therapies and new targets in this clinical setting.”
Multi-drug induction therapy followed by AHCT and lenalidomide-based maintenance therapy has been shown to offer prolonged disease control in MM, but this benefit has not been seen consistently in patients with high-risk cytogenetics. Hence, there is no clear guidance for post-AHCT maintenance therapy among patients with high-risk MM.
In this retrospective study, the researchers evaluated the outcomes of 503 patients (median age at transplant = 62 years) in the Center for International Blood and Marrow Transplant Research database. The patients had high-risk MM, defined as deletion of 17pdel, t(14;16), t(4;14), t(14;20), or chromosome 1q gain or amplification, and had undergone upfront AHCT between January 2013 and December 2018, within 12 months of diagnosis after receiving triplet novel-agent induction. Of the patients, 357 received lenalidomide alone (55% women) and 146 (33%) received bortezomib-based maintenance (55% men; 58% bortezomib alone and the rest bortezomib plus lenalidomide or another agent).
No difference was found in the pre-AHCT response rate, with approximately 60% of all patients achieving a very good partial response (VGPR) or better before transplant. Furthermore, that response was improved by AHCT, with 73% and 69% of the lenalidomide and bortezomib-based maintenance groups, respectively, achieving a VGPR or better at the 100-day mark. Non-relapse mortality at two years was similar in patients receiving lenalidomide and bortezomib-based maintenance (0% vs. 2%, respectively; p=0.16). Patients in the lenalidomide group had superior progression-free survival at two years compared with those in the bortezomib-based maintenance group (75% vs. 63%; p=0.009). Overall survival at two years was also superior in the lenalidomide group (93% vs. 84%; p=0.001).
The analysis showed no added benefit of bortezomib-based maintenance in patients with high-risk MM compared with lenalidomide alone. “However, there are some caveats that need to be considered: the group receiving bortezomib-based maintenance was more likely to have International Staging System stage III disease and to receive a lower melphalan conditioning dose (perhaps due to renal disease, which may be why bortezomib was favored as maintenance over lenalidomide), suggesting that they had other adverse prognostic features,” explained Dr. D’Souza. “Additionally, the bortezomib-based maintenance group was also more likely to have two or more high-risk cytogenetic features.” Patients in the bortezomib-based group were also more likely to have received induction therapy with VCD (bortezomib, cyclophosphamide, and dexamethasone; 29% vs. 17% in the lenalidomide-based maintenance arm; p<0.01) compared with RVD (lenalidomide, bortezomib, and dexamethasone) induction (67% vs. 82%; p<0.01) prior to AHCT.
She noted further that “the groups had important differences, suggesting a selection bias regarding which patients got bortezomib-based or double maintenance. While we adjust for all these factors in the multivariate analysis, we cannot completely overcome them without conducting a prospective randomized study.”
Study limitations include its retrospective design. Due to the lack of prospective randomization, the analysis was subject to inherent selection bias, including in the choice of post-transplant maintenance therapy. The study population included both 1q gain and amplification, which the researchers were not able to further delineate. Further, as the majority of patients received single-agent maintenance therapy, the study cannot address whether dual bortezomib and lenalidomide maintenance therapy may be an optimal strategy in patients with high-risk MM.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Bumma N, Dhakal B, Fraser R, et al. Impact of bortezomib-based versus lenalidomide maintenance therapy on outcomes of patients with high-risk multiple myeloma [published online ahead of print, 2023 Apr 6]. Cancer. doi: 10.1002/cncr.34778.
