Clinical Research in Western Africa: Efficacy and Safety of a Phase II Study of R-CHOP in First-Line DLBCL in Senegal

Background: Diffuse large B cell lymphoma (DLBCL) is the most frequent adult Non Hodgkin Lymphoma (NHL) subtype. DLBCL gold standard treatment associates CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and Rituximab for a total of 6 to 8 cycles leading to an ORR of 83% (including 75% of CR and uCR, (Coiffier B, et al). Little is known about NHL in Africa, except for the high incidence of Burkitt lymphoma in children. DLBCL in adults have also been related to a close association with various infectious agents (Naresh K, et al). Yet, difficulties including low access to health care, use of cytopuncture instead of nodal biopsy, non-respect of dose intensity, cost of drugs including CD20 monoclonal antibodies and absence of supportive care (including G-CSF) lead to poor prognosis for patients with DLBCL (overall response rate (ORR) <30%) (S Diop et al). The Senegal Government has built a national anti-cancer program, focusing on prevention and improvement of diagnosis and treatment. Our hypothesis was that the insurance of prompt and accurate diagnosis, as well as the availability of standard treatment, would improve ORR in Senegalese patients diagnosed with DLBC. Recently, a phase1/2 in Malawi showed that R-CHOP could be feasible and safe in HIV+ DLBCL patients (Kimani S, et al).

Methods: This prospective single arm non-randomized phase 2 clinical trial was performed at Dakar University Hospital. Eligible patients were adults (18-70 years old) with newly DLBCL, an ECOG-PS of 0-2, absence of HIV, HCV or HBV active infection and absence of CNS involvement. Our hypothesis was to obtain an ORR of 70% including 60% of CR or Cru (Cheson criteria 1999). Eligible patients received IV Rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1.4 mg/m² at Day 1 and oral prednisone 60 mg/m² (Day 1 to Day 5) every 21 days for 6 cycles. G-CSF was given at 5 µg/kg for 4 days (D8 to D11). The primary study endpoint was ORR at the end of treatment; secondary study endpoints were CR and CRu after 6 cycles of R CHOP, treatment toxicity, PFS, respect of treatment intensity. Whole CT scan as well as surgical nodal biopsy were mandatory. DLBCL diagnosis was confirmed by retrospective central pathology review as well as review of biopsies via an international telepathology platform using the software i-Path.

Findings: Between July 2018 and May 2022, 69 patients admitted with a clinical presentation suggestive of lymphoma were investigated with at least one biopsy, DLBCL diagnosis was confirmed for 30 of them, thus enrolled in the study. Their median age was 43 years old (range 18-64), 14 (46.6%) were women, 17 (56.6%) had stage III-IV DLBCL. The International prognostic index was 2 or higher in 23 (77%). Patients completed a median of 6 therapeutic cycles. Grade 3 or 4 hematological toxic effects were rare (one anemia, one neutropenia) but blood counts were not performed between treatment courses. One patient was hospitalized for gastroenteritis.

The ORR at the end of treatment was 69 % for the whole population including 57% of CR or uCR. Of 7 (23%) deaths, 6 were due to lymphoma progression and one to unknown cause. With a median follow-up of 19.9 months, OS and PFS at 24 months were 79.9% and 73.8%, respectively (Image 1).

Interpretation: Clinical Research is feasible in Western Africa. R CHOP therapy is safe and efficacious in HIV negative patients in Senegal, leading to similar responses as observed in high-income countries. These results should encourage health authorities to increase access to health care in order to improve the treatment of cancer.

This clinical trial was supported by the French National Institute (INCA).