Bendamustine in multiple myeloma

Abstract

The advent of high-dose melphalan with autologous stem-cell transplantation (ASCT), the availability of novel agents such as thalidomide, lenalidomide (immunomodulatory drugs or IMiDs) and bortezomib (proteasome inhibitor) and improvements in supportive care have allowed to increase overall survival in multiple myeloma (MM) patients; nevertheless, MM remains an incurable pathology. For this reason, newer agents are required for continued disease control. Bendamustine is an old drug rediscovered in the last decade. In fact, its unique mechanism of action with structural similarities to both alkylating agents and antimetabolities, but which is not cross-resistant to alkylating agents, has reawakened interest in the use of this drug in the treatment of MM. Studies have proven the safety and efficacy of bendamustine administered alone or in combination with new drugs in both upfront and relapse/refractory settings of MM patients, including those with renal impairment. Moreover, bendamustine has been successfully used as conditioning for autologous stem-cell transplantation. Finally, the use of bendamustine does not compromise peripheral blood stem-cell collection. This drug is generally well tolerated, with the majority of adverse events being due to myelosuppression. Non-haematological adverse events are infrequent and usually mild.

ALKBH7 drives a tissue and sex-specific necrotic cell death response following alkylation-induced damage

“…Chemotherapeutic alkylating agents are known to cause bone marrow toxicity and myelosuppression through cell death of hematopoietic precursors and differentiated mature bone marrow cells. 51 , 52 , 53 Moreover, we have previously shown that mouse bone marrow is highly sensitive to alkylation-induced cytotoxicity. 48 , 49 , 54 , 55 Indeed, we observed that bone marrow cellularity in WT or Alkbh7 −/− mice was decreased as early as 2 h after MMS treatment with continuing depletion of red blood cells, megakaryocytes and myeloid precursors throughout the MMS exposure period (data not shown).…”

Novel agents in the treatment of multiple myeloma: a review about the future

“…Bendamustine is a well-known alkylating agent initially developed in the 1960s, which has more recently been under increasing investigation for its potential utility in the treatment of MM [ 88 ]. Bendamustine acts as a classical alkylating agent of the nitrogen mustard class by inducing cell cycle arrest and promoting apoptosis via the alkylation of DNA [ 88 ].…”

“…Bendamustine is a well-known alkylating agent initially developed in the 1960s, which has more recently been under increasing investigation for its potential utility in the treatment of MM [ 88 ]. Bendamustine acts as a classical alkylating agent of the nitrogen mustard class by inducing cell cycle arrest and promoting apoptosis via the alkylation of DNA [ 88 ]. Recent trials have demonstrated the efficacy of bendamustine, in combined regimens, among broader cohorts of myeloma patients, and in particular among those with relapsed and/or refractory disease [ 89 ].…”

Retreatment with Bendamustine-Bortezomib-Dexamethasone in a Patient with Relapsed/Refractory Multiple Myeloma

“…Bendamustine is a well-tolerated agent with a double mechanism of action, alkylating and antimetabolite, with proved effectiveness in treatment of relapsed/refractory [10, 11] and newly diagnosed multiple myeloma [12, 13] and in a relapsing/refractory setting [14–19]. In rrMM it can be used as single agent combined to dexamethasone, but a synergistic effect has been demonstrated when associated with bortezomib.…”