Use of Doublet Maintenance (Bortezomib-Lenalidomide) Vs Monotherapy Lenalidomide As Maintenance Therapy Post-Transplant of Patients with High-Risk Cytogenetics Myeloma

Background:

Maintenance treatment plays an important role in the management of multiple myeloma (MM) by improving overall response and survival rates. Clinical trials have demonstrated that lenalidomide maintenance after autologous stem cell transplant (ASCT) in MM leads to improved progression-free survival (PFS) and overall survival (OS). It is important to note, however, that patients with high-risk multiple myeloma (HRMM) do not reap the same survival benefits from lenalidomide (R) maintenance as those with standard risk. Currently, there is no established standard of care for post-transplant maintenance in HRMM, although some institutions use doublet maintenance, typically involving bortezomib and lenalidomide (VR), in this subgroup. Our objective is to evaluate the efficacy and impact on survival in this group by comparing VR vs R in this retrospective study.

Methods:

A multi-center retrospective study in collaboration with US Myeloma Innovations Research Collaborative (USMIRC) involving MM patients ≥ 18 to compare the effectiveness of VR vs R in HRMM patients as maintenance therapy post ASCT from January 2009 to January 2024 in real-world practice. HRMM was defined as deletion 17p, t(14;16), t(4;14), and t(14;20), with or without chromosome 1q gain. We conducted exploratory analysis, using the chi-square test to compare percentages, t-test to compare means, and the log-rank test to estimate PFS and OS.

Results:

We conducted a review of 71 patients who met the eligibility criteria for this cohort,50 (70.4%) received R alone, while 21 (29.6%) received VR maintenance therapy. The median follow-up duration was 91.2 months (range: 70.3-100). The median age for the two groups (VR vs R) was 59 (range: 38-95) and 59 (range: 33-74) respectively, (p > 0.9). The distribution of stage III Revised International Staging System (R-ISS) was 29% VS 30% (p = 0.6), IgG isotype was 67% vs 58% (p = 0.6), double-hit was 57% vs 62% (p > 0.9), and the presence of extramedullary disease was 9.5% vs 8% in the patients that received VR and R, respectively. The induction therapy mainly consisted of triplet therapy, with 95% and 92% of patients receiving it in the VR group and the R group, respectively (p > 0.9). The most common triplet regimen used as induction therapy was RVD (Lenalidomide, Bortezomib, dexamethasone) in both cohorts, with 81% and 68% of patients in the VR and R groups, respectively.

The overall response rate (ORR) post-induction was 100% vs 96% (p=0.4), and the proportion of patients achieving ≥ very good partial response (VGPR) was 67% vs 70% (p=0.4) for the VR and the R group, respectively. Following ASCT at day 100, the ORR was 100% in both groups, and the proportion of patients achieving ≥ VGPR was 90.4% vs 96% (p=0.4) in VR vs R, respectively. The median PFS was 34 months (95% CI: 12-NA) vs 25 months (95% CI: 21-40) (p>0.9) in VR and R, respectively. The median OS was 98 months (95% CI: 53-NA) vs 91 months (95% CI: 70-NA) (p=0.4) in VR and R, respectively. There was no treatment-related mortality at day 100 post-transplant.

Conclusions:

This study found that patients with HRMM who received VR for maintenance post ASCT did not demonstrate significant differences in terms of PFS and OS compared to R. While the study sample size is limited for comparison, there is a need for large prospective trials and the utilization of newer treatments for maintenance therapy, such as anti-CD38 monoclonal antibodies or BCMA-directed therapies, in this subset.

Atrash:Janssen: Honoraria; Karyopharm: Research Funding; Amgen: Research Funding; GSK: Research Funding. Ahmed:Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.