Bendamustine in Combination with Gemcitabine and Vinorelbine As Salvage Regimen for Relapsed or Refractory Peripheral T-Cell Lymphomas: A Retrospective Single Center Experience

Introduction. The prognosis of non-Hodgkin lymphomas arising from mature T-lymphocyte is generally dismal, especially in the relapsed/refractory (rr) setting where the 3-year overall survival (OS) rate ranges from 20 to 30% (Bellei et al. Haematologica 2018; Chihara et al. BJH 2017). Currently, there is no established standard second-line treatment for nodal peripheral T-cell lymphomas (PTCL). Durable remissions are usually achieved through salvage treatment followed by consolidation with allogeneic hematopoietic stem cell transplantation (alloHSCT). Increasing the response rate to salvage therapy is crucial to expand the pool of patients eligible for transplantation. The aim of this retrospective study was to evaluate the efficacy of the combination of bendamustine with gemcitabine and vinorelbine (BeGeV) in rr PTCL.

Methods. This was an observational single-center retrospective study including consecutive adult patients affected by rrPTCL who received at least one cycle of BeGeV at Humanitas Research Hospital between January 2017 and January 2024. All the histological slides were reviewed by two experienced hematopathologists (AB, RD). Diagnoses were rendered according to the World Health Organization (WHO) Classification 2022 and the International Consensus Classification (ICC). The BeGeV regimen consisted of bendamustine, gemcitabine, vinorelbine, and corticosteroids as previously described, (Santoro et al. JCO 2016) with the only substitution of prednisone 100 mg per day on days 1 to 4 with dexamethasone 20 mg per day on days 1 to 4. Up to 4 cycles were administered. Dose reductions up to 50% were adopted based on patient age and/or fitness at the treating physician's discretion. Response evaluation according to Lugano criteria was performed after 2 cycles (interim evaluation), after last treatment cycle and/or as clinically indicated.

Results. From our electronical health records, we identified 20 rrPTCL patients treated with BeGeV combination and evaluable for response. Histologic subtypes included: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) (n = 10, 50%), peripheral T-cell lymphomas of T-follicular helper (PTCL-TFH) origin (n=6, 30%) - consisting of 5 nodal TFH cell lymphoma, angioimmunoblastic-type (WHO 2022)/follicular helper T-cell lymphoma, angioimmunoblastic-type (ICC 2022) and 1 “nodal TFH cell lymphoma, NOS (WHO 2022)/follicular helper T-cell lymphoma, NOS (ICC 2022) -, systemic anaplastic large cell lymphoma (sALCL) (n=3, 15%), subcutaneous panniculitis-like T-cell lymphoma (n=1, 5%). Median age was 64 years (range 48-83 years), and 70% were male. All patients but one (95%) were either refractory or early relapsed (i.e., <12 months) after last line of therapy. Most patients (75%) received only one previous line of treatment before BeGeV initiation. Initial regimens were as follows: CHOP/CHOEP (n=19), BV-CHP (n=1). International Prognostic Index (IPI) scores at time of BeGeV initiation were low (n=7), low-intermediate (n=4), high-intermediate (n=6), high (n=3).

BeGeV led to a response in 14 (70%) patients, including 8 (40%) complete remission (CR). The BeGeV combination showed inferior response (ORR 50%, CR 20%) in PTCL-NOS compared to PTCL-TFH (ORR 100%, CR 60%) and sALCL (ORR 100%, CR 66%).

Consolidation strategies encompassed: 5 alloHSCT, 1 autoHSCT, 1 radiotherapy. All the six patients in partial remission received other treatments including BV (n=4), DHAP (n=1), and enrollment in a clinical trial (n=1). Eventually, half of them received alloHSCT (2 patients after BV and 1 after DHAP regimen). Among the 6 patients refractory to BeGeV, 4 patients were deemed ineligible to further treatments, while 2 patients responded to BV salvage and were consolidated with alloHSCT. Median follow-up for the whole cohort was 38.6 months (range 1-82). Median PFS and OS were 3.5 and 8.6 months, respectively. At 12 months, PFS was 36.7%, whereas OS attained 45.9%.

Consistent with treatment response, also survival analyses were influenced by histological subtypes. Median PFS and OS were not reached for entities other than PTCL-NOS, compared to 2.6 and 5.3 months for PTCL-NOS, respectively.

Conclusion. Although limited by the small number of patients and the retrospective nature, this study provides preliminary data supporting further assessment of the BeGeV regimen as a bridge to alloHSCT in rrPTCL, especially in PTCL-TFH and sALCL subgroups.

Balzarotti:Roche: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding; Beigene: Research Funding; Takeda: Speakers Bureau; Eli Lilly: Honoraria; Gilead: Honoraria, Speakers Bureau; GenMab: Speakers Bureau; Novartis: Honoraria; Kiowa Kirin: Speakers Bureau. Carlo-Stella:Genmab: Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Humanitas University, Milano (Italy): Current Employment; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Sanofi, ADC Therapeutics: Consultancy; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Takeda: Honoraria; Sanofi, ADC Therapeutics, Celgene/Bristol-Myers Squibb, Karyopharm Therapeutics, Roche, Novartis, Scenic Biotech, Janssen Oncology, Merck Sharp & Dohme, SOBI, AbbVie, Genmab, AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Scenic Biotech: Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca, Celgene/Bristol-Myers Squibb, Incyte, Janssen Oncology, Takeda, Novartis, ADC Therapeutics, Roche, Gilead, SOBI, Merck Sharp & Dohme: Honoraria; ADC Therapeutics, Roche, Sanofi: Research Funding. Santoro:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy; EISAI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; Abb-vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Astrazeneca: Speakers Bureau; Arqule: Speakers Bureau; Lilly: Speakers Bureau; Beigene: Speakers Bureau; Novartis: Speakers Bureau; Sandoz: Speakers Bureau; Sanofi: Consultancy.