A research article that reports on "A Phase 2 Study of Nivolumab Combined with Ibrutinib in Patients with Diffuse Large B-cell Richter Transformation of CLL" was published in the journal Blood Advances this week and provides some encouraging data for a population that is very challenging to treat.
This research is based on a hypothesis that asks "if combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing."
"Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. Standard dose ibrutinib was initiated from cycle 2 onwards and continued daily until progression. A total of 24 patients with RT with a median age 64.5 years (range, 47-88) were enrolled."
This cohort of patients with DLBCL Richter Transformation (RT) included patients who were heavily pre-treated. Patients had received a median number of 3 prior CLL/RT therapies. "Ten patients (42%) had received prior treatment for RT and thirteen patients (54%) had received a prior BTKi."
There was an overall response rate (ORR) of 42%. The median Duration of Response (DOR) was 15 months and Overall Survival (OS) was "25 months for responding patients" with a median OS of 13 months.
The authors compared these results against two other therapies for RT:
a) standard first-line treatment for RT which "generally includes traditional chemoimmunotherapy regimens (such as R-CHOP, O-CHOP, R-DHAP, R-EPOCH, OFAR) and these lead to responses in 30-60% of previously untreated RT with a median survival of less than one year" and
b) venetoclax with dose-adjusted R-EPOCH, a recent phase 2 study (VR-EPOCH). In "26 patients with RT (24/26 were previously untreated for RT) with a median of 1 prior line of therapy for CLL, the overall response rate was 62% with a median PFS [progression free survival] of 10.1 months and median OS of 19.6 months.
Nivolumab combined with Ibrutinib produced "comparable results for the patients who were treatment-naïve for RT, without the use of intensive chemotherapy. We treated 14 patients who were previously untreated for RT with a median of 2 prior CLL therapies. We noted an ORR of 50% (7/14) with a median DOR of 10.1 months and median OS of 24.1 months."
"Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option."
To read more details in the abstract, visit:
ashpublications.org/bloodad...
To read the full research article, select the 'pdf' option on the abstract page.
Nitin Jain, Jayastu Senapati, Beenu Thakral, Alessandra Ferrajoli, Philip A Thompson, Jan A. Burger, Sreyashi Basu, Tapan M. Kadia, Naval G. Daver, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Erin M. Parry, Catherine J. Wu, Joseph D. Khoury, Carlos E. Bueso-Ramos, naveen garg, Xuemei Wang, Wanda Lopez, ANA AYALA, Susan M. O'Brien, Hagop M. Kantarjian, Michael J Keating, James P Allison, Padmanee Sharma, William G. Wierda; A Phase 2 Study of Nivolumab Combined with Ibrutinib in Patients with Diffuse Large B-cell Richter Transformation of CLL. Blood Adv 2022; bloodadvances.2022008790. doi: doi.org/10.1182/bloodadvanc...
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