Characterized by clonal proliferation of bone marrow cells, multiple myeloma can be treated effectively, if detected early. Several treatment regimens have been suggested, however, the efficacy and tolerability of these drugs along with resistance to treatment developed with time remain a challenge.1 A combination of dexamethasone with proteasome inhibitor like bortezomib  has been used in several studies involving relapsed and refractory multiple myeloma. A recently published article on the long-term follow-up Phase 3 randomized study conducted by Southwest Oncology Group and National Clinical Trials (SWOG S0777) demonstrated how bortezomib plus lenalidomide and dexamethasone can be used in treating newly diagnosed multiple myeloma patients effectively.2 

The study was conducted in 460 adult patients with newly diagnosed multiple myeloma and had measurable disease (as per CRAB criteria where C stands for elevated calcium levels, R suggests renal impairment, A suggests anemia, and B refers to bone involvement). 

Patients were enrolled between 2008 and 2012 and received either eight 21-day cycle of bortezomib (1.3 mg/m3, intravenous on days 1, 4, 8, and 11), lenalidomide  (25 mg, oral once daily on days 1 to 14), and dexamethasone (20 mg, oral on days 1, 2, 4,5, 8, 9, 11, and 12) or six 28-day cycles of lenalidomide (25 mg, oral, once daily for 21 days) and dexamethasone (40 mg, oral, once a week). 

Results at the end of 7 years after this induction therapy demonstrated that the bortezomib+lenalidomide+dexamethasone combination was effective than lenalidomide+dexamethasone combination with improved progression-free survival (41 months versus 29 months, p=0.003), improved overall survival (not reached at 84 months versus 69 months, p=0.0114), and improved response duration (50 months versus 39 months, p=0.0175).

There was added benefit seen in patients who did not receive any transplant as well as who were not candidates for transplant following treatment with bortezomib+lenalidomide+ dexamethasone combination than the other group. Added benefit was also seen in younger patients (<65 years old) following treatment with bortezomib+lenalidomide+dexamethasone combination.

Patients treated with the combination of bortezomib, lenalidomide, and dexamethasone had better objective response rate (90.2%, 74.9% with VGPR or better) than those treated with combination of only lenalidomide and dexamethasone (78.8%, 53.2% with VGPR or better) as given in Table 1.

Table 1: - Responses received from assessable patients

Although the safety profiles of both treatment groups were similar, more patients in the bortezomib+lenalidomide+dexamethasone group (34.6%) experienced neurological adverse event than the patients treated with lenalidomide+dexamethasone combination (11.3%). Thus, the study demonstrates that bortezomib, lenalidomide, and dexamethasone combination therapy is beneficial and has tolerable safety profile in newly diagnosed multiple myeloma.

References:

1. Das S et al. Multiple myeloma: Challenges encountered and future options for better  treatment. Int J Mol Sci. 2022;23(3):1649.

2. Durie BGM et al. Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT). Blood Cancer J. 2020;10(5):53.