Subcutaneous Rituximab Given to Patients for Other Indications Than CD20+ B-Cell Lymphoma: A Monocentric Study of 20 Cases

Background: Rituximab (R) is the first anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various B-cell lymphoid malignancies. Administered intravenously (IV), it has been shown to be also efficient to treat other hematologic situations such as Epstein-Barr virus (EBV) reactivation, especially after hematopoietic stem cell transplantation (HSCT), or immune thrombocytopenic purpura (ITP). Finally, survivals of younger patients with CD20-positive Philadelphia-negative acute lymphoblastic leukemia (ALL) are significantly increased when combining IV-R with chemotherapy. Recently, a subcutaneous (SC) formulation of R (SC-R) has been approved for B-cell lymphoma that provides a highly-concentrated fixed dose of rituximab with the advantages of reducing treatment times and nursing workload and potentially providing greater comfort and convenience for patients and lesser dosing errors, shorter preparation time or reduced drug wastage for pharmacy dispensers. At our knowledge, there is no published data addressing the tolerance and the efficacy of SC-R given to patients with other indications than CD20+ B cell lymphoma.

Patients and Methods: We have retrospectively analyzed all cases who received at our center at least one dose of SC-R but with no lymphoma indication. Three situations were considered: EBV reactivation (post transplantation or not), ITP or ALL treatment. All patients received their first(s) dose(s) of R IV (375mg/m²/injection) and a switch to SC-R (1400mg/injection) was realized only if they didn't experience grade 3 or 4 adverse event (AE) with IV formulation. Our rules is to provide R (IV+SC) weekly, up to 4 doses for ITP (in case of platelets counts <30000/mm³ with no response to corticosteroids or immunoglobulin) and EBV reactivation (in case of 2 positive PCR > 4 log10 number of viral DNA copies), while GRAALL schedule is followed for R administration in CD20+ ALL patients. Tolerance of SC-R (mainly infusion related or late-onset neutropenia (LON)) was appreciated using National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 and any grade 3 or 4 AE related to SC-R was sufficient to stop treatment. Success of SC-R was defined by either a documentation of a negative EBV PCR or absence of ALL relapse or platelets counts reaching at least 100000/mm3.

Results: Between February 2016 and June 2017, 20 patients (male n=17) with a median age of 60 years old (range: 33-76) received SC-R in our institution. Overall, 102 R including 58 SC-R were administered with a median of 3 R (range: 2-26) and 2 SC-R (range: 1-16) injection per patient, respectively. The median follow-up from the last SC-R administration was 4.4 months (range: 0.2-11.2 months).

No grade 3/4 infusion related reaction were documented in this series while 4 out of 16 assessable cases presented with LON at a median of 45 days (range: 44-70) after the last SC-R injection. Neutropenia lasted a median of 6 days (range: 4-9) with the help of GCSF and was not responsible for complication.

Eleven cases received SC-R for EBV reactivation (including 8 after allogeneic transplant and 3 in a context of aplastic anemia) with a median of 3 R (IV+SC, range: 1-4) and 2 SC-R (range: 1-3) injections. One patient died of concomitant invasive fungal infection and was not evaluable for efficacy. All of the ten other patients were documented with negative EBV PCR after treatment.

Four patients received SC-R during ALL first line treatment with a median of 11 R (IV+SC, range: 3-26) and 6 SC-R (range: 1-16) injections. Two patients have received more than the number of R infusion scheduled (17 and 26) because of high toxicity related to the chemotherapy and it was chosen to deliver a maintenance therapy with vincristine/SC-R and prednisone. None of the four ALL patients had relapsed so far at 2, 8, 18 and 20 months from diagnosis with a median follow up of 13 months (2-20).

Five patients received SC-R for ITP with a median of 3 R (IV+SC, range: 3-4) including 2 SC-R (range: 1-3) injections. Three patients obtained platelets count improvement within a median of 28 days (19-48) and none relapsed so far.

Conclusion: SC-R seems to demonstrate a comparable efficacy/safety profile as IV-R when given to patients for other indications than CD20+ B-cell lymphoma. There should be no restriction to use SC-R for these patients in the future as it may improve quality of care for both patient and health providers.