Obinutuzumab and miniCHOP for unfit patients with diffuse large B-cell lymphoma. A phase II study by Fondazione Italiana Linfomi

Abstract

To evaluate activity and safety of obinutuzumab-miniCHOP (Ga101-miniCHOP) combination in older patients with Diffuse Large B-Cell Lymphoma (DLBCL) unfit to receive full dose immunochemotherapy. Materials and Methods: We conducted a Simon's two-stage phase II multicenter trial to investigate response rate (primary endpoint) and safety of six courses of Ga101-miniCHOP in older patients with DLBCL (≥65 years), prospectively defined as unfit according to a simplified Comprehensive Geriatric Assessment (sCGA). Results: Overall, 34 patients were enrolled (median age 82 years; range 68-89), with 27 out of the 33 eligible patients completing all six planned courses. Complete Remission (CR) rate was reported in fourteen patients (42%). After a median follow-up of sixteen months, the two-year Progression Free and Overall Survival (PFS and OS) were 49% (95% Confidence Interval (CI), 28 to 67) and 68% (95% CI, 49 to 81), respectively. The most frequent grade 3-4 adverse event was neutropenia in thirteen patients (26%). Conclusions: Based on the observed CR rate, study accrual was interrupted due to the very low probability of demonstrating the initial study hypothesis that Ga101-miniCHOP could improve results of historical data obtained with R-miniCHOP in this group of patients. Nonetheless, results achieved with the 33 treated patients confirm activity and good tolerability of the Ga101-miniCHOP regimen for older unfit adult patients with DLBCL.

Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients

“…[100] Replacing rituximab with the 3 rd -generation antibody obinutuzumab did not improve outcomes. [101] BR is often viewed as palliative, though in a prospective sCGAguided trial focused on frail patients, it resulted in 51% 2-year OS, comparable to 59% observed after R-mini-CHOP. [89] Other studies reported less favorable results for bendamustine combinations, with median OS ≤1 year.…”

“…R‐mini‐CHOP, R‐CNOP, or R‐GCVP have been recommended by guidelines as viable curative options [100]. Replacing rituximab with the third‐generation antibody obinutuzumab did not improve outcomes [101]. BR is often viewed as palliative, although in a prospective sCGA‐guided trial focused on frail patients, it resulted in 51% 2‐year OS, comparable to 59% observed after R‐mini‐CHOP [89].…”

Antibody Therapies for Large B-Cell Lymphoma

“…26 Similar data of efficacy and safety were reported in a phase II trial of Fondazione Italiana Linfomi (FIL) in elderly unfit patients treated with GA101 plus dose-reduced CHOP. 27 Tafasitamab Tafasitamab (MOR208) is an anti-CD19 humanized Ab enhanced by the modification of two amino acids in the Fc region, which increases its affinity for Fcγ receptors. It mediates Ab-dependent cellular phagocytosis, Abdependent cellular cytotoxicity via NK cells, and direct cytotoxicity.…”

Geriatric assessment in older patients with a hematologic malignancy: a systematic review

“…The median sample size of the studies was 100 (range, 25-869), and the me(di)an age of included patients ranged from 58 to 86 years. Eight studies focused on acute myeloid leukemia and/or myelodysplastic syndromes, [19][20][21][22][23][24][25]27 two on chronic lymphocytic leukemia, 28,29 13 on lymphoma, [30][31][32][33][34][35][36][37][38][39][40][41][42] seven on multiple myeloma, [42][43][44][45][46][47][48] and 15 studies included various hematologic malignancies. [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] The median number of domains addressed in the geriatric assessment was four (range, 2-9).…”

“…median age less than 68 years old, or more than one third of the patients younger than 65 years old); 22,27,41,43,46,48,50,58,59 these studies were assessed as not being fully representative of the target cohort of the average older patients with a hematologic malignancy. Similarly, eight studies focused on a very specific treatment 20,23,24,31,51,55,56,60 which we considered as not fully representative of our target population. Overall, the duration of follow-up was sufficient but in nine studies the followup rate was less than 90% 24,30,46 or the adequacy of followup was not reported.…”