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Lenalidomide-Induced Warm Autoimmune Hemolytic Anemia

Our Lady of Mercy Medical Center, Bronx, NY

To the Editor:

Cases of warm autoimmune hemolytic anemia (AIHA) due to treatment with lenalidomide (Revlimid; Celgene Corporation, Summit, NJ) have not been previously reported.

A 69-year-old woman receiving lenalidomide as part of a clinical trial for the treatment of diffuse large B-cell lymphoma was admitted to hospital with weakness, shortness of breath, and a hematocrit of 21% (hemoglobin 7.6 gm/dL). The peripheral blood reticulocyte count was 277 corresponding to a percentage of 12.4% of all RBCs. Stool guaiac test was negative and laboratory tests confirmed hemolysis. Her indirect antiglobulin test (IAT) and direct antiglobulin or Coomb's test ( DAT) were positive and an eluate demonstrated a panagglutinin. She was diagnosed with myelosuppression due to lenalidomide as well as new onset warm autoimmune hemolytic anemia (AIHA). Her symptoms and hematocrit improved rapidly subsequent to the discontinuation of lenalidomide and administration of oral prednisone for 4 days.

One month later, she presented again with a hematocrit of 17% (hemoglobin, 6 g/dL) after restarting treatment with lenalidomide. She had similar symptoms and required readmission to the hospital. There was clinical and laboratory evidence for hemolysis. IAT and DAT were positive with the eluate demonstrating a panagglutinin again. Lenalidomide was discontinued and she was started on a 7-day course of oral prednisone (60 mg daily). She was given four units of packed RBCs over 5 days and her hematocrit (hct) improved to 30% on day 5. Her DAT became weakly reactive on hospital day 5 but remained positive until day 11. The eluate was nonreactive on day 11. Her last positive IAT was reported on day 11 with all subsequent IATs remaining negative.

In addition to serologic improvement of her warm AIHA, she displayed reduced clinical evidence for hemolysis with her hemoglobin remaining stable without further RBC transfusions between days 5 and 15. After the discontinuation of lenalidomide her palpable spleen enlarged rapidly. She had increasing peripheral blood lymphocytosis and bone marrow biopsy with aspirate was consistent with progressive lymphoma on day 11, for which she was started on rituximab on hospital day 12. Treatment could not be continued due to infectious complications and she died on day 52.

Lenalidomide is approved for use in multiple myeloma and subsets of patients with myelodysplastic syndromes. Currently, we are conducting a clinical trial using lenalidomide for the treatment of non-Hodgkin's lymphoma.

AIHA has not been previously associated with lenalidomide. Drug-induced AIHA is characterized by a newly positive DAT during exposure to new medications.¹ Clinical and/or laboratory evidence of hemolysis may be subtle in many patients but significant hemolysis of the patient's own red cells may lead to life threatening anemia.² The degree of anemia that can be attributed to hemolysis due to AIHA may be hard to assess if patients are receiving medications like lenalidomide that are associated with cytopenias.

We report a first case of AIHA with warm autoantibodies during treatment with lenalidomide. However, hematologic malignancies may lead to AIHA by themselves and for our patient, evidence of any causal effect by lenalidomide was confounded by the presence of lymphoma; nevertheless, it is fair to add this case to the list of adverse outcomes after lenalidomide administration. In our patient, there was serologic and clinical improvement of AIHA soon after discontinuation of lenalidomide. When the patient was rechallenged with lenalidomide she manifested exacerbation of AIHA, which again improved with drug discontinuation. Then her lymphoma continued to progress as evidenced by increasing splenomegaly, peripheral blood lymphocytosis, and bone marrow involvement. Despite progression of her lymphoma, there was no serologic evidence for AIHA (negative IAT and DAT after day 11). Her IAT remained negative for the remainder of her hospitalization.

Authors' Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Peter H. Wiernik Celgene Celgene Celgene

REFERENCES

1. Oh YR, Carr-Lopez SM, Probasco JM, et al: Levofloxacin-induced autoimmune hemolytic anemia. Ann Pharmacother 37:1010-1013, 2003[Abstract/Free Full Text]

2. Tertian G, Cartron J, Bayle C, et al: Fatal intravascular autoimmune hemolytic anemia after fludarabine treatment for chronic lymphocytic leukemia. Hematol Cell Ther 38:359-360, 1996[CrossRef][Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Darabi, K. Articles by Wiernik, P. H. Search for Related Content PubMed PubMed Citation Articles by Darabi, K. Articles by Wiernik, P. H. Social Bookmarking                            What's this?