For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for hematopoietic cell transplantation, treatment with a combination of the anti-CD19 monoclonal antibody tafasitamab and lenalidomide was associated with high response rates, including relatively high rates of complete responses (CRs). This is according to results from a phase II trial published in Lancet Oncology by Gilles Salles, MD, PhD, of the Lyon Sud Hospital Center in France, and colleagues.
Dr. Salles told ASH Clinical News that the results of this study may have a substantial impact on clinical practice, considering this combination did not include cytotoxic chemotherapy yet was associated with a “remarkable” overall response rate and CR rate, as well as a promising progression-free survival (PFS), duration of response, and overall survival (OS). “If approved by health authorities,” said Dr. Salles, “this regimen will be a new option for patients with relapsed or refractory DLBCL – as second line of therapy for patients not eligible for transplant, or as third line.”
This multicenter, open-label study (L-MIND) enrolled 81 adult patients (median age = 72 years) from 35 academic and community hospitals in 10 countries. Participants had histologically confirmed DLBCL that relapsed after or was refractory to 1 to 3 systemic regimens (including at least one anti-CD20 therapy) and were not candidates for high-dose chemotherapy and subsequent hematopoietic cell transplantation.
Treatment consisted of intravenous tafasitamab 12 mg/kg weekly on days 1, 8, 15, and 22 of cycles 1 to 3 (with an additional dose on day 4 of cycle 1) and on days 1 and 15 of subsequent cycles, plus oral lenalidomide 25 mg/day, for up to twelve 28-day cycles. Tafasitamab monotherapy was subsequently administered in patients with stable disease or better until disease progression.
“If approved by health authorities, this regimen will be a new option for patients with relapsed or refractory DLBCL.”
—Gilles Salles, MD, PhD
Prior to study entry, all patients had previously received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), or equivalent anthracycline-containing immunochemotherapy.
At time of data cutoff, the median follow-up was 13.2 months. Thirty patients (37%) completed a total of 12 cycles of the combination regimen, and 28 patients (35%) were still receiving tafasitamab monotherapy.
During follow-up, the overall median duration of treatment exposure was 9.3 months – 6.2 months for the combination regimen and 4.1 months for tafasitamab monotherapy after lenalidomide discontinuation.
A total of 48 patients achieved at least a partial response (PR), for an objective response rate of 60%; 34 (43%) achieved a CR. The median time to an initial response, either a PR or CR, was 2 months, and responses lasted for a median of 21.7 months. Among the 14 patients who experienced a PR (18%), the median duration of response was 4.4 months, but the median duration of CR was not reached.
Approximately one-half of participants (n=39) experienced either disease progression or death during follow-up. The median PFS was 12.1 months, and 12- and 18-month PFS rates were 50% and 46%, respectively.
The median OS was not reached, and 12- and 18-month OS rates were 74% and 64%, respectively. The investigators added that, at time of data cutoff, 38% of patients (n=30) had disease that was in remission.
In the safety analysis, the most frequent grade ≥3 treatment-emergent adverse events (AEs) were:
- neutropenia (48%)
- thrombocytopenia (17%)
- febrile neutropenia (12%)
A total of 41 of the 81 patients (51%) experienced serious AEs, the most frequent of which were pneumonia (6%), febrile neutropenia (6%), pulmonary embolism (4%), bronchitis (2%), atrial fibrillation (2%), and congestive cardiac failure (2%). “Upon discontinuation of lenalidomide (either cycle 13 onward as per protocol or earlier in case of toxicities), the incidence and severity of treatment-emergent AEs decreased under tafasitamab monotherapy,” the authors added, noting that grade 3 or 4 AEs were reported in 56 of 80 patients (70%) before lenalidomide discontinuation, compared with 15 of 51 patients (29%) after lenalidomide discontinuation.
According to Dr. Salles, there were no new safety signals identified for either drug or the combination.
Limitations of the study included its open-label design, lack of a comparator arm, and the small number of patients included in the final sample. “This study also did not recruit patients whose disease had immediately failed R-CHOP therapy,” added Dr. Salles, “and the number of patients with primary refractory disease or disease refractory to their last line of therapy was limited.”
Study authors report relationships with MorphoSys, which sponsored this trial.
Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21:978-988.