Promising chemo-free treatment options in r/r DLBCL

Several novel agents and combinations are under development as alternatives to chemotherapy treatment in relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). These new agents include novel antibodies, CAR T-cell therapy, checkpoint inhibitors, immunotoxins, PI3K inhibitors, novel kinase inhibitors, BiTE, Bcl-2 inhibitors, and BTK inhibitors [1].

The poor outcomes of chemotherapy in patients with r/r DLBCL create a major unmet medical need for alternative treatment regimes. This is true for patients either eligible or ineligible for transplantation. For example, rituximab + gemcitabine and oxaliplatin (R-GemOx) in r/r DLBCL patients ineligible for autologous transplantation demonstrated a median progression free-survival time of 5 months and a median overall survival of only 10 months [2].

Prof. Marco Ladetto (University del Piemonte Orientale, Italy) discussed the use of non-chemotherapeutic agents in transplant-ineligible r/r DLBCL. Non-chemotherapeutic agents are used either alone, as a rational combination of biologicals, or in combination with chemotherapy.

Prof. Ladetto discussed 3 of the interesting treatment options currently under development:

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  • loncastuximab tesirine, a novel immunotoxin, showed durable response and an acceptable safety profile in the phase 2 LOTIS-2 trial (NCT03589469) [3];
  • glofitamab, a T-cell engaging agent, showed durable response in patients with r/r aggressive B-cell non-Hodgkin’s lymphoma in a recent phase 1 trial (NCT03075696) [4]; and
  • the combined use of tafasitamab, an anti-CD19 antibody, and lenalidomide, an immunomodulatory agent, which synergistic effects led to markedly longer median progression-free survival of 16.2 months (median follow-up 22.6 months) than chemotherapy regimens, such as R-GemOx [2,5].

Prof. Ladetto concluded, “Given the modest value of chemotherapy salvage treatments, it is reasonable to further explore the value of non-chemotherapeutic agents, either alone or in rational combinations.”

1. 
   
   1. Ladetto M. What is the role of chemo-free regimens for the treatment of R/R DLBCL? 1SS08-OD2, EHA 2021 Virtual Congress, 9-17 June.
   2. Cazelles C, et al. Leuk Lymphoma. DOI 10.1080/1428194.2021.1901090.
   3. Kahl BS, et al. Clin Can Res. 2019;25(23):6986–94.
   4. Hutchings M, et al. J Clin Oncol. 2021;39(18):1959–70.
   5. Salles G, et al. EP1201 EHA 2020 Congress, 11–21 June.

 

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Posted on 5 August 202129 February 2024