First-MIND trial: Safety of tafasitamab plus R-CHOP for newly diagnosed DLBCL

The combination of rituximab with cyclophosphamide, doxorubicin, prednisone, and vincristine (R‑CHOP) is the standard frontline treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Although R-CHOP has led to improved prognosis for many patients, around 15–20% of treatment-naïve patients have tumors with downregulated expression of CD20 and therefore have poorer responses to rituximab-containing regimens. Tafasitamab is an anti-CD19 Fc-modified monoclonal antibody therapy that enhances antibody-dependent cellular cytotoxicity and phagocytosis. Tafasitamab is currently approved by the U.S. Food and Drug Administration (FDA) in tandem with lenalidomide for treating relapsed/refractory DLBCL in patients not eligible for autologous stem cell transplant.

At the European Hematology Association (EHA)2021 Virtual Congress, David Belada presented a poster highlighting results from the First-MIND trial (NCT04134936), a phase 1b open-label trial investigating the safety and efficacy of tafasitamab plus R-CHOP or tafasitamab and lenalidomide plus R-CHOP for adult patients with newly diagnosed DLBCL. We summarize key results below.

Study design

The First-MIND trial enrolled 83 patients from 34 sites in Europe and the US. A total of 66 adult patients with newly diagnosed DLBCL were randomized 1:1 to the following treatment arms:

• Arm A: R-CHOP + tafasitamab (12 mg/kg intravenously).
• Arm B: R-CHOP + tafasitamab (12 mg/kg intravenously) + lenalidomide (25 mg orally).
• In addition, patients were given mandatory granulocyte stimulating factor prophylaxis, and for Arm B only, mandatory venous thromboembolism prophylaxis.
• Treatment consisted of a total of six 21-day treatment cycles, with dosing schedules for both treatment arms summarized in Figure 1.

Len, lenalidomide; R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; Taf, tafasitamab.
*Adapted from Belada, et al.¹

 

Eligibility criteria

Eligibility criteria for this study included adults aged ≥18 years, treatment-naïve DLBCL, an International Prognostic Index of 2–5, and an Eastern Cooperative Oncology Group performance score of 0–2.

Exclusion criteria included patients with double- or triple-hit lymphoma, transformed non-Hodgkin lymphoma, evidence of composite lymphoma, history of radiation therapy to ≥25% of the bone marrow for other diseases, history of anthracycline therapy, known central nervous system involvement, or active hepatitis B/C infection.

Results

Patient characteristics are summarized in Table 1.

Table 1. Baseline patient characteristics*

DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; PS, performance status; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone *Data from Belada, et al.1
Characteristic	Arm A: R-CHOP + tafasitamab (n = 33)	Arm B: R-CHOP + tafasitamab + lenalidomide (n = 33)
Median age, years (range)	66 (43–86)	64 (20–79)
Female, %	54.5	60.6
Ann Arbor disease stage, %
I	6.1	3.0
II	0	3.0
III	21.2	21.2
IV	69.7	72.7
Missing	3	0
IPI risk score, %
2	33.3	27.3
3	42.4	45.5
4	24.2	24.2
5	0	3
Bulky disease present, %	42.4	45.5
ECOG PS, %
0	60.6	33.3
1	30.3	57.6
2	9.1	9.1
Reference diagnosis DLBCL (central pathology review), %
DLBCL	90.9	90.9
Other	3.0	9.1
Missing	6.1	0

Primary endpoint

Over a follow-up of 18 months, the most frequent TEAEs were blood and lymphatic disorders. The relative platelet and neutrophil counts remained consistent between both treatment arms across all six cycles of treatment, however the incidences of Grade ≥3 cytopenia and thrombocytopenia were higher for patients treated with tafasitamab plus lenalidomide. In total, six patients received platelet transfusion; three patients in each arm. Grade ≥3 TEAEs are summarized in Table 2.                                                                                                                                                                                                                            

Table 2. Grade ≥3 hematologic and non-hematologic TEAEs*

R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; TEAE, treatment-emergent adverse event. *Data from Belada, et al.1
Grade ≥3 TEAE, %	Arm A: R-CHOP + tafasitamab (n = 33)	Arm B: R-CHOP + tafasitamab + lenalidomide (n = 33)
Hematologic
Neutropenia	57.6	84.8
Anaemia	21.2	27.3
Thrombocytopenia	9.1	33.3
Leukopenia	18.2	27.3
Febrile cytopenia	18.2	18.2
Lymphopenia	12.1	21.2
Non-hematologic
Diarrhea	3.0	6.1
Hypokalaemia	9.1	6.1
Peripheral neuropathy	0	3.0
Vomiting	3.0	0
Constipation	0	3.0
Asthenia	3.0	0
Fatigue	3.0	0
Stomatitis	3.0	0
Hypotension	3.0	9.1
Infusion-related reaction	0	3.0
Abdominal pain	0	3.0

• Serious TEAEs were reported in 42.4% of patients in Arm A and 51.5% of patients in Arm B.

• Three deaths were reported, none of which were attributable to tafasitamab or lenalidomide treatment.
• The median average relative dose intensity of R-CHOP was unchanged in either treatment arm, remaining at 100% throughout all six cycles of treatment.
  • A total of 21 patients experienced treatment cycle delay overall, and the percentage of patients reporting delays in each cycle are summarized in Table 3.

Table 3. Number of patients with a treatment cycle delay within each cycle*

R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. *Data from Belada at al.1
Cycle number, %	Arm A: R-CHOP + tafasitamab (n = 33)	Arm B: R-CHOP + tafasitamab + lenalidomide (n = 33)
Cycle 2	12.1	6.1
Cycle 3	3.0	0.0
Cycle 4	12.1	6.1
Cycle 5	3.0	9.1
Cycle 6	3.0	9.1

Secondary endpoints

In total, 60 patients were assessed for overall response at the end of treatment. The ORR for both arms combined was 83.3% (95% confidence interval, 71.5–91.7) and the complete remission rate was 75.0% (95% confidence interval, 62.1‒85.3).

Conclusion

Overall, the First-MIND trial demonstrated the tolerability of tafasitamab and lenalidomide in addition to R-CHOP for treatment-naïve DLBCL. No unexpected toxicity was observed, and while Grade ≥3 neutropenia frequency was higher with tafasitamab plus lenalidomide (84.8%) versus tafasitamab alone (57.6%), the incidence of febrile neutropenia was equal (18.2%). Additionally, the relative dosage intensity of R-CHOP was unaffected with the addition of both therapies. Efficacy analysis provided promising evidence for response with this triplet combination, with a combined ORR of 83.4% and complete remission rate of 75.0%.