Clinical Research in Africa: Collaborative Project between Senegal and France to Improve the Diagnosis and Therapeutic Management of Adult Lymphoma Patients

Background: Little is known about Non-Hodgkin Lymphoma (NHL) in Africa except for the high incidence of Burkitt lymphoma in children and the high association with HIV in Eastern Africa but not Western Africa. Difficulties including low access to health care, use of cytopuncture instead of nodal biopsy, cost of drugs and absence of supportive care lead to poor prognosis for NHL patients (pts) (overall response rate (ORR) <30%) (Diop et al., Bull Soc Patho Exo 2004). Meaningful lymphoma research cannot be conducted without accurate diagnosis (Naresh et al., Br J Hematol 2011). The Senegal Government has built a national anti-cancer program, focusing on prevention and improvement of diagnosis and treatment. A prospective single arm non-randomized phase 2 clinical trial was thus designed for adult pts with newly diagnosed diffuse large B-cell lymphoma (DLBCL) at Dakar (Senegal) University Hospital (DUH), in collaboration with Nancy (France) University Hospital (NUH).

Methods: Histological results of suspected lymphoma in pts likely to be included in this trial are reported here. Only non-HIV adult patients were enrolled. A first histological study was performed in the pathology department of DUH. This included biopsies that were submitted to apposition before embedding. Hematoxylin and eosin staining was performed as well as immunohistochemistry (IHC). The panel used allowed to examine the expression of the following antigens: CD20, CD79a, CD3, CD5, CD23, cyclin D1, CD30, Bcl2, CD10 and Ki67. Biopsies were reviewed via an international telepathology platform using the i-Path software and retrospectively, in NUH Pathology department, by sending paraffin-embedded blocks on site.

Findings: Between July 2018 and May 2022, 70 pts admitted with a clinical presentation suggestive of NHL were evaluated with a surgical biopsy, 31 of whom being confirmed with a diagnosis of DLBCL or equivalent as T-cell/histiocyte-rich large B cell LBCL, and thus eligible for the therapeutic trial. Median age of the 70 pts was 42 years old (18-70) and 32% were female. Other hematological diagnoses were Hodgkin lymphoma, small B-cell lymphoma, T-cell lymphoma, unclassed lymphoma and histiocytosis. There was no Burkitt lymphoma. Non-hematological diagnoses were achieved for 14 pts: lipoma, tuberculosis, reactive adenitis or metastasis of solid neoplasia. In nearly half of all cases, diagnosis was obtained without IHC, notably due to non-hematological diagnoses. In nearly half of all cases, the diagnosis was obtained without IHC. When IHC was used, CD20 and CD3 were mainly used to establish the diagnosis. The median time to obtain pathology results was 31 days. Thirty-one cases were diagnosed with the help of I-Path. Currently, 17 biopsies have been reviewed at NUH with diagnosis concordance in 71% of cases. The 5 inconsistent diagnoses were 2 NHL ultimately classified as adenocarcinoma, 1 reactive adenitis being in fact DLBCL and 2 T-cell/histiocyte-rich LBCL diagnosed as respectively DLBCL and small B-cell lymphoma.

Interpretation: This is a large cohort of consecutive surgical biopsies performed in Senegal for lymphoma suspicion, showing the distribution of lymphoma in Western Africa and more interestingly, demonstrating that an accurate diagnosis is possible locally. The current hindrances in lymphoma diagnosis include basing treatment decisions on fine needle aspiration cytology in a large proportion of cases, poor quality histology or complete lack of IHC in cases where biopsies are performed, limited number of hematopathologists and lack of discussion between hematopathologists. In this study, systematic surgical biopsy, homogenous IHC staining procedures, electronic interaction between hematopathologists and retrospective review of biopsies have contributed to a huge improvement of the quality of diagnosis.

Moulin:Sanofi: Other: Congress invitation. Thieblemont:Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Hospira: Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Bayer: Honoraria; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Broséus:Astra Zeneca: Consultancy, Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria. Feugier:AstraZeneca, Janssen, Abbvie, Beigene, Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Congress Invitations.