TY - JOUR
T1 - Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: Results from the CAVALLI phase 1b trial
AU - Zelenetz, Andrew D.
AU - Salles, Gilles
AU - Mason, Kylie D.
AU - Casulo, Carla
AU - le Gouill, Steven
AU - Sehn, Laurie H.
AU - Tilly, Herve
AU - Cartron, Guillaume
AU - Chamuleau, Martine E. D.
AU - Goy, Andre
AU - Tam, Constantine S.
AU - Lugtenburg, Pieternella J.
AU - Petrich, Adam M.
AU - Sinha, Arijit
AU - Samineni, Divya
AU - Herter, Sylvia
AU - Ingalla, Ellen
AU - Szafer-Glusman, Edith
AU - Klein, Christian
AU - Sampath, Deepak
AU - Kornacker, Martin
AU - Mobasher, Mehrdad
AU - Morschhauser, Franck
PY - 2019/5/2
Y1 - 2019/5/2
N2 - Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2 1 and MYC 1 ) DLBCL patients (87.5%; n 5 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study.
AB - Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2 1 and MYC 1 ) DLBCL patients (87.5%; n 5 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065507396&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30850381
U2 - https://doi.org/10.1182/blood-2018-11-880526
DO - https://doi.org/10.1182/blood-2018-11-880526
M3 - Article
C2 - 30850381
SN - 0006-4971
VL - 133
SP - 1964
EP - 1976
JO - Blood
JF - Blood
IS - 18
ER -