Background: Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Methods: Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. Results: The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. Conclusions: This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS.

Venetoclax Plus Intensified Chemoimmunotherapy as a Bridge to Allogeneic Stem Cell Transplantation in Richter Syndrome: Report of Two Cases / E. Derenzini, A. Cignetti, V. Tabanelli, D. Gottardi, E. Gerbino, A. Vanazzi, S. Sammassimo, A. Maraglino, F. Melle, G. Motta, D. Malengo, E. Omodeo Salè, L. Bonello, R. Pastano, S. Pileri, F. Carnevale Schianca, C. Tarella. - In: HEMATOLOGY REPORTS. - ISSN 2038-8330. - 16:4(2024 Dec), pp. 795-803. [10.3390/hematolrep16040075]

Venetoclax Plus Intensified Chemoimmunotherapy as a Bridge to Allogeneic Stem Cell Transplantation in Richter Syndrome: Report of Two Cases

E. Derenzini
Primo
;
A. Vanazzi;F. Melle;L. Bonello;C. Tarella
Ultimo
2024

Abstract

Background: Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Methods: Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. Results: The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. Conclusions: This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS.
Richter syndrome; chronic lymphoid leukemia; venetoclax; chemotherapy; GMALL regimen
Settore MEDS-09/B - Malattie del sangue
Settore MEDS-09/A - Oncologia medica
dic-2024
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1151099
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