August 2023

Thomas R. Collins

Patients with autoimmune cytopenias had longer durations of response after induction treatment with rituximab when rituximab was continued as maintenance therapy compared with no rituximab maintenance following treatment, according to a study published in the British Journal of Hematology.

The study is the first to examine rituximab as maintenance in immune thrombocytopenia (ITP), offering the first published data on its benefits, said James Bussel, MD, of Weill Cornell Medical College in New York. Another study on this approach for ITP will likely be finished within a year or earlier, he said.

Rituximab maintenance, giving much longer-term depletion of B cells, could be offered to patients more widely, Dr. Bussel noted. He believes this approach is not commonly used for ITP. “It could be very helpful,” he said.

Early reports of patients with ITP who were treated with rituximab indicated a 40% to 60% response rate after four infusions. However, longer-term follow-up found that lasting remission was seen only in 21% of adults with chronic ITP. Re-treatment with rituximab in these patients did not lead to remission in any of them.

This study included patients with challenging autoimmune cytopenias – ITP, autoimmune hemolytic anemia (AIHA), and Evans syndrome, which involves the co-existence of ITP and AIHA. They were treated at Weill Cornell Medicine’s Platelet Disorders Center, but some received induction or maintenance treatment elsewhere.

The 16 people enrolled in the study had a response to an initial, four-infusion regimen of rituximab, subsequently relapsed, then responded to another four-infusion induction of rituximab. After the second induction regimen, maintenance with rituximab consisted of a maximum of six 375 mg/m² doses administered at three- or four-month intervals. The maintenance was started about three to four months after the second induction.

These requirements were chosen so that prolonged response times could be attributed to the maintenance rather than a new induction treatment.

The patients’ age at diagnosis ranged widely, from six months to age 69, with a mean age at diagnosis of 21.3 years. Seven of the patients received dexamethasone with rituximab and one patient received mycophenolate mofetil with rituximab maintenance.

After the re-induction, 15 patients had a complete response (CR), and one achieved a partial response (PR). The median duration of response after the first induction was 19.5 months, but the median duration of response with maintenance was 43 months (p<0.01). At the time of data cutoff, nine patients had ongoing responses – eight achieved a CR and one achieved a PR.

The median duration of response for patients with ITP only was 64 months, 57 months for patients with AIHA, and 26 months for patients with Evans syndrome.

Three of the patients developed hypogammaglobulinemia, one of whom also developed sepsis. “The patient who developed sepsis is an important caution that all patients must be carefully followed and IVIG [intravenous immunoglobulin] replacement instituted in the event of clinically significant hypogammaglobulinemia,” researchers noted. “Maintenance likely increases the risk of hypogammaglobulinemia, especially if induction is given with dexamethasone.”

Researchers acknowledged the number of patients was small and the trial was single arm. They also said questions remain, such as for whom rituximab maintenance might be appropriate and whether lasting, treatment-free remission is possible. However, Dr. Bussel said the only obvious patients who might not be appropriate for rituximab maintenance are those with concerns about the efficacy of vaccinations.

“It is hypothesis-generating,” researchers noted, “that maintenance rituximab may be as effective in ITP as it is in lymphoma.”