Cost-effective rituximab-based treatment keeps CAD at bay for years
Study: Therapy combines immune-targeting medication with chemotherapy
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A short course of rituximab, combined with chemotherapy agents and corticosteroids, can keep primary cold agglutinin disease (CAD) under control for many years, at a lower cost and with manageable side effects, according to a study of seven patients in Japan.
“Rituximab-based chemoimmunotherapy elicited durable responses with an acceptable safety profile in patients with CAD, highlighting the potential of fixed-duration therapy as a feasible and economically favorable option,” researchers wrote.
Chemoimmunotherapy refers to a combination of chemotherapy agents and immune-targeting medications, such as rituximab.
The study, “Durable responses and favorable cost-effectiveness of rituximab-based chemoimmunotherapy for primary cold agglutinin disease,” was published as a correspondence in the journal Blood Research.
Red blood cells targeted in CAD
In CAD, the immune system produces self-reactive antibodies that react against red blood cells in cold temperatures, leading to their destruction, a process known as hemolysis. The complement cascade, a part of the immune system, is known to contribute to CAD-related hemolysis.
There are two main types of CAD: primary CAD, which occurs without a known cause, and secondary CAD, which occurs due to other diseases, most often infections and blood cancers.
Treatment for primary CAD can be broadly divided into therapies that promote the death of antibody-producing immune B-cells and those that suppress the activation of the complement cascade.
The former includes rituximab (marketed as Rituxan and Mabthera, with biosimilars available), administered alone or in combination with chemotherapy agents and other immune-targeting medications.
The latter includes Enjaymo (sutimlimab-jome), the only approved CAD medication, which targets the complement system. While effective, “it requires continuous administration and is expensive,” the researchers wrote.
Previous studies have reported durable responses in CAD patients treated with rituximab-based chemoimmunotherapy, but most did not comprehensively screen for the presence of blood cancers as potential causes of the condition. They may, therefore, have included both cases of primary and secondary CAD, which have different treatment approaches.
All patients responded to rituximab treatment
To assess the safety and efficacy of rituximab-based chemoimmunotherapy in individuals with primary CAD, the researchers retrospectively analyzed data from seven people with CAD that was not caused by cancer or infections.
Tests to screen for potential causes of CAD included a genetic test that looked for the L265P mutation in the MYD88 gene, which is a common cause of a type of slow-growing blood cancer called Waldenström’s macroglobulinemia.
Of the seven patients, four were men and three were women, with ages ranging from 48 years to 85 years. Two did not require treatment because they had normal levels of hemoglobin — the protein in red blood cells that carries oxygen — and no symptoms.
Of the other five, four had received blood transfusions before starting chemoimmunotherapy.
Four of those requiring treatment received reduced-dose rituximab, along with the chemotherapy agents cyclophosphamide, doxorubicin, and vincristine, and the corticosteroid prednisolone — a regimen known as R-CHOP. The remaining patient received R-bendamustine, a combination of rituximab plus the chemotherapy drug bendamustine.
All five treated patients responded. Four achieved a complete response, while the remaining person showed a partial response. A complete response was defined as normal levels of hemoglobin, absence of symptoms, no need for blood transfusions, and normalization of blood levels of hemolysis markers.
Although [Enjaymo] provides clinical benefits, the treatment’s limited cost-effectiveness reflects its extremely high price and the need for continuous administration. In contrast, the fixed-duration rituximab-based regimen employed in the present study achieved durable responses with a more favorable cost-effectiveness.
Overall, participants took a median of three weeks to achieve a partial response and about five months to attain a complete response. Responses lasted for a median of 90 months (about 7.5 years).
In terms of safety, the most serious side effect was moderate to severe neutropenia (a low number of neutrophils, a type of immune cell) in four of the treated patients (80%). Two patients (40%) had a mild infection. One patient developed stomach cancer later, though it is unclear whether this was related to the treatment.
The researchers then used economic models to compare this fixed-duration chemoimmunotherapy to Enjaymo. They found that the fixed-duration chemoimmunotherapy regimen was more cost-effective than Enjaymo, which needs lifelong administration every two weeks. The high cost of continuous treatment made it less favorable when compared with a therapy given for a defined period.
“Although [Enjaymo] provides clinical benefits, the treatment’s limited cost-effectiveness reflects its extremely high price and the need for continuous administration,” the researchers wrote. “In contrast, the fixed-duration rituximab-based regimen employed in the present study achieved durable responses with a more favorable cost-effectiveness.”
While the study was small, it suggests that, in carefully selected people with primary CAD, a finite course of rituximab-based chemoimmunotherapy can provide long-lasting responses, with manageable side effects, and at a lower overall cost than continuous treatment with Enjaymo.
