Impact of Absolute Lymphocyte Count on Efficacy and Toxicity of T-Cell Engagers in Non-Hodgkin's Lymphoma

Introduction: The management of relapsed/refractory non-Hodgkin's lymphoma (NHL) has been significantly impacted by the approval of T-cell engagers (TCE). Three TCEs have been approved for use in NHL: mosunetuzumab, epcoritamab, and glofitamab. A growing concern is T-cell exhaustion with the use of T-cell directed therapies such as TCEs and chimeric antigen receptor T-cell (CAR-T). It is known that decreased absolute lymphocyte count (ALC) prior to lymphodepletion and CAR-T therapy impacts efficacy and theoretically could impact acute and long-term toxicities. It is unknown whether baseline ALC has this same impact in patients receiving TCEs, particularly as the TCE requires T-cell engagement as its mechanism of action. This study aimed to evaluate whether baseline ALC impacted outcomes in patients receiving TCEs.

Methods: A single-center, retrospective review of 55 patients who received a TCE for NHL was conducted. TCEs in this analysis could include: mosunetuzumab, epcoritamab, and glofitamab. Baseline ALC was evaluated on cycle 1 day 1 of treatment. The Lugano response criteria was utilized to evaluate an overall response rate (ORR). The ASTCT consensus grading was utilized for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Descriptive statistics were utilized for demographics, toxicity, and efficacy outcomes. Chi-square and Fischer's exact were utilized for comparisons across groups.

Results: Of the 55 patients, 30 patients (54.5%) received mosunetuzumab, 15 (27.3%) received epcoritamab, and 10 (18.2%) received glofitamab. The median age was 71 years (range: 38-100), the majority were Caucasian (90.9%) and male (69.1%). The median number of prior lines of therapy was 4 (range: 1-4). The most common diagnoses were diffuse large B-cell lymphoma (56.4%) and follicular lymphoma (20%). Herpes simplex virus prophylaxis was administered to 80% of patients and Pneumocystis jiroveci pneumonia prophylaxis was administered to 50.9% of patients. ALC was < 0.5 K/UL in 12 patients (21.8%), > 0.5 K/UL in 20 patients (36.4%), and unknown in 23 patients (41.8%).

CRS occurred in 17 patients (30.9%); the majority of events were grade 1-2 (94.1%). The only grade 3 CRS occurred with mosunetuzumab. ICANS occurred in 5 patients (9.1%); there was only 1 (20%) grade 3-4 ICANS event. Four of the ICANS events occurred with epcoritamab therapy and 1 occurred with mosunetuzumab therapy. Twenty-nine patients (49%) experienced at least one infection during the treatment period; 27.2% of patients had a treatment interruption due to infectious symptoms or complications. Hospitalization due to infection occurred in 14 patients (25.4%) with a median length of stay being 6 days (range: 2-45 days). Only 1 patient (7.1%) required transfer to ICU-level of care due to infectious complications. Partial response or better occurred in 33 patients (60%); response was unknown in 6 patients (10.9%).

In the whole patient population, CRS occurred in two (16.7%) patients with a baseline ALC of < 0.5 versus 8 (40%) patients with a baseline ALC of > 0.5 K/UL and 7 (30.4%) patients with unknown baseline ALC (p=0.397). ICANS occurred in 1 (8.3%) patient with ALC < 0.5 K/UL, 3 (15%) patients with ALC > 0.5 K/UL, and 1 (4.3%) patient with an unknown ALC (p=0.519). ORR was not significantly different between the 3 ALC groups (p=0.536). Overall, there was no significant difference in CRS, ICANS, or ORR between patients with ALC < 0.5 K/UL and those with ALC > 0.5 K/UL. Similarly, there was no difference in CRS, ICANS, or ORR among mosunetuzumab, epcoritamab, and glofitamab.

Conclusion: The occurrence of CRS and ICANS occurred at a low frequency, and the majority of events were low grade. In this small patient population, ALC did not seem to impact rates or severity of CRS or ICANS or therapeutic response, regardless of TCE administered. This differs from the information currently known about ALC and CAR-T therapy and should be confirmed with a larger patient population. If confirmed in larger, multi-institution or in head-to-head studies, this could shift the treatment paradigm in favor of TCEs over CAR-T in patients with low ALC.

Ahmed:Kite, a Gilead Company: Research Funding; Bristol Myers Squibb: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding. Tun:The University of Kansas: Current Employment. Hoffmann:Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Other: Travel; ADC, Janssen, Pharmacyclics, BeiGene, Novartis, Astra-Zeneca, Abbvie, Kite, TG: Consultancy, Honoraria. Lutfi:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees.