Combination of low-dose rituximab, bortezomib and dexamethasone for the treatment of autoimmune hemolytic anemia

Abstract

Autoimmune hemolytic anemia (AIHA) therapy may be associated with severe complications such as diabetes, hypertension, obesity, osteoporosis, peptic ulcers, infection, and some other diseases. To reduce those effects, we used low-dose rituximab, bortezomib and dexamethasone (LowR-BD regimen) to treat AIHA. The purpose of this study was to evaluate the efficacy and safety of this regimen. Seven patients with warm AIHA (wAIHA) admitted from March 2020 to October 2020 were treated with LowR-BD regimen: Rituximab 100 mg by intravenous infusion on day 1 combined with bortezomib 1.3 mg/m 2 by subcutaneous injection on day 2 plus dexamethasone 20 mg by intravenous infusion on days 2, 3. Clinical efficacy and safety were assessed at the regular reexamination of relevant indicators and follow-up. After 4 cycles of the LowR-BD regimen, the overall response rate (ORR) was 85.71% with a complete response (CR) of 28.57% and a partial response (PR) of 57.14%. After a median follow-up of 12 (range 7–13) months, 5 patients achieved CR and 2 patients had PR status, including 1 patient who did not respond to LowR-BD treatment and reached CR after using methylprednisolone combined with cyclophosphamide. One patient relapsed and achieved PR after retreatment of 2 cycles LowR-BD regimen. The patients tolerated the treatment well and did not complain of apparently adverse reactions except a patient with Sjogren's syndrome and bronchiectasis who developed a severe infection during treatment. Low-dose rituximab combined with bortezomib and dexamethasone is effective and relatively safe in patients with wAIHA.

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

“…In a retrospective series of adults who received 6 cycles of bortezomib plus dexamethasone, 6 of 8 patients responded following a median of 2 (range, 1-4) cycles ( 123 ). A small, prospective study found response to a combination of bortezomib, low-dose rituximab, and dexamethasone in 6 of 7 patients with refractory wAIHA ( 124 ).…”

“…Bortezomib-based combination regimens, addressed above, might also be used in emergencies based on the high response rates reported in small series and relatively low toxicity ( 123 , 124 ). Administration of an ESA can be a useful supplement in a hemolytic crisis ( 1 , 103 ).…”

Sutimlimab for the Treatment of Cold Agglutinin Disease

“…Furthermore, bortezomib monotherapy has shown some benefit in a small, prospective trial, and recent results from a warm-antibody AIHA study seem to indicate that this benefit might be improved by using bortezomib in combinations. 65 , 66 Two cases of success with the anti-CD38 monoclonal antibody daratumumab have been reported in patients with refractory CAD, 67 , 68 but systematic studies have not been published.…”

“…Among B‐cell‐directed approaches, the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has shown highly promising results in a retrospective series, 64 and a prospective BTKi trial in CAD is warranted. Furthermore, bortezomib monotherapy has shown some benefit in a small, prospective trial, and recent results from a warm‐antibody AIHA study seem to indicate that this benefit might be improved by using bortezomib in combinations 65,66 . Two cases of success with the anti‐CD38 monoclonal antibody daratumumab have been reported in patients with refractory CAD, 67,68 but systematic studies have not been published.…”

Development of New Drugs for Autoimmune Hemolytic Anemia

“…Bortezomib has also been combined with other agents to treat AIHA, in the first-line setting with the hope of minimizing steroid exposure [ 171 ] as well as in the refractory setting in case reports and retrospective studies [ 172 , 173 , 174 ], most commonly in combination with rituximab. A combination of rituximab and bortezomib would synergically increase plasma-cell and B-cell depletion [ 174 ].…”