Tafasitamab plus lenalidomide, rituximab boosts PFS in follicular lymphoma

The addition of tafasitamab (tafa) to lenalidomide and rituximab (len+R) significantly improves progression-free survival (PFS) in patients with relapsed or refractory (R/R) follicular lymphoma (FL), as shown in a phase III study presented at ASH 2024. The safety profile of this combination is manageable and consistent with expected toxicities.

“This study is the first to validate combining two mAbs (anti-CD19 with anti-CD20) in the treatment of lymphoma,” said lead author Dr Laurie Sehn from the BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada.

“Tafa+len+R can be administered in community as well as academic settings and represents a potential new standard of care option for patients with R/R FL,” she added.

Sehn and her team randomized 548 patients with R/R FL and ECOG PS ≤2 to receive either tafa 12 mg/kg (n=273) or placebo (n=275) on days 1, 8, 15, and 22 of cycles 1‒3 and days 1 and 15 of cycles 4‒12 with standard dosing of len+R for up to 12 28-day cycles.

Baseline characteristics were comparable between the two treatment arms (median age 64 years, 55-percent male, 79-percent intermediate- or high-risk Follicular Lymphoma International Prognostic Index; 83-percent high tumour burden per GELF criteria). [ASH 2024, abstract LBA-1]

The median number of prior lines of treatment was 1, 45 percent had ≥2 prior lines, 32 percent had disease progression within 24 months, and 43 percent were refractory to prior anti-CD20 mAb.

Disease progression

At data cutoff, patients treated with tafa and placebo received a median of 12 and 11 cycles of treatment, 19 percent and 15 percent were still receiving therapy, and 81 percent and 84 percent discontinued treatment due to completion (54 percent and 43 percent) or disease progression (11 percent and 31 percent), respectively.

Over a median follow-up of 14.1 months, tafa added to len+R significantly reduced the risk of progression, relapse, or death relative to placebo (median PFS 22.4 vs 13.9 months; hazard ratio [HR], 0.43, 95 percent confidence interval [CI], 0.32‒0.58; p<0.0001).

The PFS benefit derived from tafa persisted in all prespecified subgroups, including patients with POD24, those refractory to prior anti-CD20 mAb, and those receiving several prior lines of treatment.

For the other outcomes, the PET-CR rate (49.4 percent vs 39.8 percent; p=0.029) and objective response rate (83.5 percent vs 72.4 percent; p=0.0014) were higher with tafa than placebo. Duration of response also improved with tafa (median 21.2 vs 13.6 months; hazard ratio [HR], 0.47, 95 percent CI, 0.33‒0.68; p<0.0001), as did time to next treatment (median not reached vs 28.8 months; HR, 0.45, 95 percent CI, 0.31‒0.64; p<0.0001).

OS data were immature, but a trend favouring tafa was observed (HR, 0.59, 95 percent CI, 0.31‒1.13).

Treatment-emergent adverse events (AEs) were similar between arms (99 percent vs 99 percent), as were grade 3 or 4 AEs (71 percent vs 69.5 percent) and serious AEs (36 percent vs 32 percent). The most common grade 3 or 4 AEs were neutropenia (40 percent vs 38 percent), pneumonia (8 percent vs 5 percent), thrombocytopenia (6 percent vs 7 percent), decreased neutrophils (6 percent vs 7 percent), COVID-19 (6 percent vs 2 percent), and COVID-19 pneumonia (5 percent vs 1 percent).

Discontinuation due to treatment-emergent AEs occurred in 11 percent and 7 percent of patients in the tafa and placebo arms, respectively. Additionally, 15 patients (5.5 percent) in the tafa arm and 23 (8.5 percent) in the placebo arm died during the study.