Efficacy and Safety Profile of Novel Alkylators in Combination Regimens for Patients with Multiple Myeloma: A Review of Literature

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.5626-5626
• Main Authors: Aslam, Shehroz, Riaz, Rida, Rafae, Abdul, Malik, Mustafa Nadeem, Jose, Jemin Aby, Shah, Zunairah, Abu Zar, Muhammad, Qureshi, Anum, Kamal, Ahmad, Ijaz, Awais, Khan, Ali Younas, Malik, Saad Ullah, Anwer, Faiz
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-110144

Introduction Bendamustine (B) and Melflufen (Mel) are Non-Food and Drug Administration (FDA) approved novel alkylators that exert their cytotoxic effects by cross-linking of DNA strands via alkylation, resulting in the inhibition of mitotic checkpoints leading to cell death. We report published literature on efficacy and safety of combination regimens of novel alkylators in patients (pts) with multiple myeloma. Methods We performed a comprehensive literature search on articles published after 2012 using following search engines (Pubmed, Embase, Cochrane, Web of Science and Clinical Trials.gov). We included both phase II, III studies and summarized our data using absolute values and percentages. Results Bendamustine: We included four phase II studies of B involving 217 pts. One hundred seventy-six pts had relapsed and refractory multiple myeloma (RRMM) while 41 pts had newly diagnosed multiple myeloma (NDMM). The overall response rate (ORR) was 71.75 % and 92% in RRMM and NDMM pts respectively. In a phase II trial (n=41), NDMM pts who were not eligible for autologous stem cell transplant (ASCT) were included. B (80 mg/m2 on days 1 and 2), bortezomib (V) (1.3 mg/m2 on days 1, 8 and 15) and dexamethasone (D) (20 mg on days 1, 2, 8, 9, 15 and 16) were given for every 28 days for 8 cycles. In 39 evaluable pts, the ORR was 92% with complete response (CR) in 17% pts, very good partial response (VGPR) in 59% pts, and partial response (PR) in 21% pts. The most common grade 3 and 4 adverse effects (AEs) were leukopenia (12%), thrombocytopenia (7%), neutropenia (15%), and fatigue (12%). In a phase II trial (n=50), pts with RRMM were included. B (75mg/m2 on days 1 and 2), Lenalidomide (R) (25mg on 1-21 days) and D (40mg/20mg on days 1, 8, 15, 22) were given in a 4-weekly cycle for 6 cycles. In 45 evaluable pts, the ORR was 88.9% with CR in 15.5% pts, VGPR in 40% pts, and PR in 33.3% pts. The 2-year progression-free survival (PFS) and the overall survival (OS) were 42% and 76% respectively. The most common grade 3 and 4 AEs were neutropenia (74%), leukopenia (70%), thrombocytopenia (38%), anemia (20%), and infections (14%). In another phase II trial (n=94) pts with RRMM were included. B (60 mg/m2 versus 100 mg/m2 on days 1-8 of 28 day cycle), thalidomide (T) (100 mg on days 1-21) and D (20 mg on days 1,8,15 and 22 of 28 day cycle) were given. The dose of 100 mg/m2 was later discontinued due to cytopenias. In 54 evaluable pts, the ORR was 46.3% with CR in 1.9% pts, VGPR