Immunosuppressive therapy leads to transfusion independence for nearly 40% of patients with myelodysplastic syndrome

ATLANTA — Immunosuppressive therapy helped nearly 40% of patients with myelodysplastic syndrome achieve transfusion independence, according to study results presented at ASH Annual Meeting and Exposition.

Patients who achieved response or transfusion independence survived longer, results showed.

All patients with lower-risk myelodysplastic syndrome experience primary or secondary failure of hypomethylating agents, erythropoiesis-stimulating agents or lenalidomide (Revlimid, Celgene), creating a need for other active therapies.

Immunosuppressive therapy has demonstrated activity among patients with lower-risk myelodysplastic syndrome; however, it is not used often.

Maximilian Stahl, MD, resident physician and instructor of medicine at Yale Cancer Center, and colleagues assessed clinical outcomes and predictors of response among patients with myelodysplastic syndrome treated with immunosuppressive therapy. The patients underwent treatment at one of 11 centers in the United States or Europe.

Researchers used modified 2006 International Working Group myelodysplastic syndrome criteria to assess responses and red blood transfusion independence.

The analysis included 367 patients (median age at diagnosis, 65 years; range, 15-95; 63% male) who received immunosuppressive therapy. Twenty-three percent of patients had low-risk disease as measured by International Prognostic Scoring System criteria; 68% had intermediate-1-risk disease, and 9% had either intermediate-2- or high-risk disease.

The majority (67.8%; n = 249) of patients received at least one prior therapy (median, 1; range, 0-7), the most common of which were erythropoiesis-stimulating agents (43%) and hypomethylating agents (29%). Slightly more than 40% (n = 149) of patients who only received prednisone were excluded from the response and survival analysis.

Among the other patients, the most commonly used immunosuppressive therapies were anti-thymocyte globulin (46%), cyclosporine (11%) and tacrolimus (5%).

Of the 114 patients for whom response criteria were reported, 13.2% (95%, 7.8-21.1) achieved complete remission, 5.3% (95% CI, 2.2-11.6) achieved partial response, and 31.6% (95% CI, 23.4-41) achieved hematologic improvement. This equated to a 45% overall response rate.

Another 38% (95% CI, 29.8-48.2) of patients demonstrated stable disease, and 11.4% (95% CI, 6.5-19.1) had progressive disease.

More than one-third (38.3%) of patients achieved transfusion independence.

Stahl and colleagues reported median OS from time of immunosuppressive therapy initiation of 47.2 months (95% CI, 35-69.4) in the entire cohort.

Patients who achieved a response — complete remission, partial response or hematologic improvement — had significantly longer median OS than those who did not respond (not reached vs. 26 months; P = .0004).

Patients who achieved transfusion independence with immunosuppressive therapy survived longer than those who remained transfusion dependent (not reached vs. 52 months).

Univariate analysis showed female sex (HR = 0.6; P = .04), as well as higher-risk International Prognostic Scoring System score (HR for standard scoring system = 1.9, P = .01; HR for revised scoring system = 1.3; P = .02), predicted shorter OS.

However, multivariate analysis showed only one variable — bone marrow blast greater than 5% — remained a statistically significant predictor of OS (HR = 6.6; P < .0001).

A univariate analysis of response revealed an association between SF3B1 mutational status and lower response rate (OR for mutated vs. nonmutated = 0.2; P = .04). However, multivariable analysis identified no predictive factors for response.

Researchers observed no association between response to immunosuppressive therapy and patient age, myelodysplastic syndrome risk score, prior transfusion dependence, type of immunosuppressive therapy used, presence of a paroxysmal nocturnal hemoglobinuria or large granular lymphocyte leukemia clone and human leukocyte antigen DR15 positivity, or mutations in the TP53, IDH1/2, ASXL1 or SF3B1 genes.

“To our knowledge, this is largest reported cohort of patients with myelodysplastic syndrome treated with immunosuppressive therapy,” Stahl and colleagues wrote. “[Although] we confirmed that immunosuppressive therapy is associated with an ORR of 45% and leads to transfusion independence in 39% of patients, we could not confirm the predictive value of several previously described biomarkers of response. Apart from SF3B1 mutations, which appear to negatively affect response to IST, no other factors were identified that predicted response to immunosuppressive therapy.” – by Mark Leiser

For more information:

Stahl M, et al. Abstract 422. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosures: Stahl reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.