Jain, Tania

Abstract Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure. Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids. CRS and neurotoxicity are more common and more severe with chimeric antigen receptor T-cell therapy (CAR-T). The fact that CAR-T cannot be discontinued on demand adds a layer of complexity to the management of related toxicities of this therapy. Tocilizumab, an interleukin-6 receptor blocker, is used to treat severe CRS from CAR-T, whereas corticosteroids remain the mainstay for neurotoxicity management. Although effective, these drugs carry a high price tag, and we review the available data on cost-effectiveness of these agents, keeping in mind that median follow-up on most of these studies is limited and that long-term data on durability of response remain to be seen.

AbstractMantle cell lymphoma is characterized by relapse and progressive disease, despite initial response to chemoimmunotherapy. We conducted a systematic review and meta‐analysis to determine the efficacy of rituximab maintenance (RM) therapy in patients with mantle cell lymphoma. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials from database inception through November 1, 2017. Only full‐text articles were included. Prespecified data elements were extracted from each trial. Outcomes of interest included progression‐free survival (PFS) and overall survival (OS). The overall effect was pooled using the Der Simonian‐Laird random effects model. Three randomized controlled trials and four observational studies met our inclusion criteria and were identified in the analyses. Six studies compared RM therapy to observation, and one compared RM therapy to interferon alfa. Meta‐analysis evaluating outcomes of patients treated after ASCT revealed that RM improved for both PFS (HR = 0.33, 95% CI = 0.23‐0.49) and OS (HR of death = 0.35, 95% CI = 0.17‐0.69). A second meta‐analysis of studies evaluating outcomes of patients who are ASCT‐ineligible treated with anthracycline‐based induction therapy revealed that RM improved PFS (HR = 0.38, 95% CI = 0.25‐0.58). There is a paucity of data on the role of RM in ASCT‐ineligible patients and those with relapsed disease. Overall, RM therapy appears to improve PFS and OS in previously untreated patients with mantle cell lymphoma who undergo induction chemoimmunotherapy followed by ASCT.

Abstract A dynamic approach to use bisphosphonates according to biomarkers of bone metabolism is presented in the Z-MARK study by Raje and colleagues. This is a major step forward toward a rational approach to bisphosphonate usage. Clin Cancer Res; 22(6); 1301–3. ©2016 AACR. See related article by Raje et al., p. 1378