Dexamethasone, rituximab, and cyclophosphamide as primary treatment of Waldenström macroglobulinemia: final analysis of a phase 2 study

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

“…158 In both examples, the ability of a specific agent (e.g., oxaliplatin, cyclophosphamide) but not one of its alike (e.g., cisplatin, melphalan) to drive ICD can be explained by the differential activation of ER stress (and hence differential exposure of CALR in the course of RCD). 100,[157][158][159] Well established ICD inducers include commonly employed anticancer chemotherapeutics such as: (1) (6) bortezomib, a proteasomal inhibitor approved for the therapy MM and mantle cell lymphoma (MCL); [171][172][173][174][175][176][177][178][179][180][181] (7) cyclophosphamide, a DNA-alkylating agent approved for use in patients with chronic myeloid leukemia (CML), AML, ALL, chronic lymphocytic leukemia, MM, ovarian carcinoma, breast carcinoma, mycosis fungoides, lymphoma, neuroblastoma, and retinoblastoma; 177,[182][183][184][185][186][187][188][189][190][191] and (8) oxaliplatin, a platinum-derivative licensed for the therapy of advanced colorectal carcinoma in combination with 5-fluorouracil and folinic acid. 156,157,[192][193][194][195][196][197][198] Moreover, there is some evidence that microtubule-targeting agents including taxanes and vinca alkaloids (which are commonly used for the treatment of multiple carcinomas) can stimulate ICD.…”

Waldenström Macroglobulinemia: Review of Pathogenesis and Management

“…In the recent update of this study, time to treatment failure was 35 months, and many of the relapsing patients were still sensitive to rituximab based regimens. The 8-yr OS rates were 100%, 55%, and 27% for the low, intermediate, and high risk groups, respectively 31 . In a randomized trial with 48 treatment-naïve WM patients who were randomly assigned to either CHOP or R-CHOP, R-CHOP showed significantly higher ORR (91% vs. 60%, p =0.0188) and 2-year PFS rate (78% vs. 47%, p =0.0241) 32 .…”

“…In a study by Ghobrial et al with 26 treatment-naïve WM patients, 6 cycles of bortezomib combined with rituximab showed ORR 100%, 1-year PFS and OS rates of 75% and 96%, respectively 39 . RCyD combination showed a median PFS of 35 months and 5-year OS rate of 62% 28,31 . Similar to RCyD, bortezomib, dexamethasone, and rituximab (BDR) combination in two studies showed ORR 90–96%, PFS rate 40–80%, and OS rate 80–100% with significant improvement in BM involvement and serum IgM levels 40,41 .…”

New developments in the management of Waldenström macroglobulinemia

“…Patients who relapse after DRC are found to be still sensitive to rituximab. The regimen appears to be safe in both short and long terms 40,41…”