Venetoclax-failed monotherapy in B-lymphoproliferative neoplasms responded to combination of venetoclax with immunochemotherapy: A report of two cases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F20%3AN0000049" target="_blank" >RIV/00098892:_____/20:N0000049 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0145212620300783" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0145212620300783</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Venetoclax-failed monotherapy in B-lymphoproliferative neoplasms responded to combination of venetoclax with immunochemotherapy: A report of two cases

Original language description

Venetoclax (ABT-199), an inhibitor of B-cell lymphoma 2 (BCL-2) protein, has been approved for the treatment of chronic lymphocytic leukaemia (CLL) and in late-phase clinical trials for B-cell non-Hodgkin's lymphoma (B-NHL), multiple myeloma, acute myeloid leukaemia and myelodysplastic syndrome [[1], [2], [3], [4]]. However, patients who failed under venetoclax treatment have a very poor prognosis, as shown for CLL [5,6]. Several therapeutic approaches have been suggested for these patients: ibrutinib, idelalisib, chemotherapy, rituximab, allogeneic stem cell transplantation, and CAR-T cell therapy [[5], [6], [7]]. In ibrutinib naive CLL, ibrutinib should be the first choice [7], however, reduced responses to given alternative regimens were reported in ibrutinib-pre-treated patients [5,6]. Therefore, novel treatment strategies and effective drug combinations should be suggested for patients at risk of early failure or treatment resistance on venetoclax. We describe here two patients with B-lymphoproliferative neoplasms, who failed on venetoclax monotherapy, and achieved a good overall response after adding a combination of rituximab and cyclophosphamide to venetoclax. Both patients signed the combination therapy informed consent; the study was conducted in accordance with the Declaration of Helsinki. In both patients, the combination of venetoclax with immunochemotherapy resulted in the clinically significant and almost year-long regression of lymph nodes and bone marrow tumour cell infiltration, respectively. Our first case was a CLL patient (male, 56 years at diagnosis, Binet A, isolated 6q deletion, unmutated IGHV, medical history included prostatectomy due to benign prostate hypertrophy in 2008 and total hip arthroplasty in 2008) diagnosed in 2008 according to iwCLL2018 [8]. This relapsed/refractory (R/R) patient was heavily immunochemotherapy pre-treated with intolerance and progression on ibrutinib (Fig. 1A). After venetoclax monotherapy initiation, the patient reached partial remission (PR) according to iwCLL2018 criteria [8] with residual abdominal lymph nodes and progression free survival (PFS) of 21 months. After an additional eight months of asymptomatic slow progression on venetoclax monotherapy, the patient began to subjectively suffer from abdominal pressure, hiccups and post-meal vomiting; an abdominal ultrasound detected a massive lymphadenomegaly (up to 12 cm in diameter), which filled the hepatorenal space, epigastrium and paraaortal space. The venetoclax monotherapy had to be interrupted several times (< 7 days) due to neutropenia G3 according to the Common Terminology Criteria for Adverse Events (CTCAE) [9], infections treatment and/or medical interactions.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30205 - Hematology

Project

<a href="/en/project/NV16-32339A" target="_blank" >NV16-32339A: Impact of functional polymorphisms influencing inflammation and oxidative stress on outcome and selection of treatment in chronic lymphocytic leukemia</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů