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Oupatient Lenalidomide Desensitization For Delayed Hypersensitivity Reactions In 5 Patients With Multiple Myeloma
AB276 Abstracts
951
Dual Hypersensitivity To Oxaliplatin Revealed Following Rapid Drug Desensitization: A History Of Anaphylaxis and New-Onset Hemolytic Anemia Dr. Jared Silver, MD, PhD1, Dr. Timothy Kyin, MD1, Dr. Mariana C. Castells, MD, PhD, FAAAAI2; 1Brigham and Women’s Hospital, Boston, MA, 2Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. RATIONALE: Oxaliplatin is a third generation platinum chemotherapy for colorectal cancer within FOLFOX regimens. After multiple exposures, hypersensitivity reactions are reported and some are IgE-mediated, including anaphylaxis. Co-existing type II hypersensitivity may also develop. METHODS: A 56yo male with metastatic colon cancer treated with FOLFOX manifested disease progression and with first re-exposure to oxaliplatin developed palmar erythema and with second re-exposure developed anaphylaxis (flushing, chest pressure, and dyspnea). Oxaliplatin skin testing was positive. The patient completed six oxaliplatin desensitizations using the BWH 3-bag 12-step protocol. Breakthrough reactions included fevers, chills, palmar erythema, back pain, and SOB. During the seventh desensitization, he presented with fever, rigors, palpitations, dizziness, and EKG changes. Desensitization was discontinued. RESULTS: EKGs demonstrated ST/T-wave abnormalities without troponin leak. Labs demonstrated 1.8 gm/dL decrease in hemoglobin (9.8 to 8.0 gm/dL, normal range 13.5-18), normal tryptase (5.6 ng/ml (reference range <11.5)), elevated total bilirubin (from 1.0 mg/dL to 3.1 (normal range 0-1)), elevated LDH (865 U/L (normal range 135-225)), reduced haptoglobin (<8mg/dL (normal range 30-200)), and positive direct Coombs testing. Platelets decreased by 117 K/ml to 142 (normal range 150-450). He was diagnosed with oxaliplatin-induced autoimmune hemolytic anemia. Oxaliplatin was discontinued. CONCLUSIONS: To our knowledge, this is the first reported case of a patient with type I hypersensitivity to oxaliplatin manifesting a type II hypersensitivity during chemotherapy desensitization. All desensitization providers should remain vigilant not only for direct drug toxicity and breakthrough type I hypersensitivity, but also for alternative forms of hypersensitivity which contraindicate agent-specific desensitization.
952
TUESDAY
Oupatient Lenalidomide Desensitization For Delayed Hypersensitivity Reactions In 5 Patients With Multiple Myeloma Dr. Min Jung Lee, MD1, Dr. Paige G. Wickner, MD2, Dr. Robert Schlossman, MD3, Dr. Paul Richardson, MD3, Dr. Jacob Laubach, MD3, Dr. Mariana C. Castells, MD, PhD, FAAAAI4; 1Brigham & Women’s Hospital, Boston, MA, 2Brigham & Women’s Hospital, Chestnut Hill, MA, 3Dana Farber Cancer Institute, Boston, MA, 4Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. RATIONALE: Lenalidomide is an immunomodulatory agent used in the treatment of multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Rash has been reported in nearly 30% of treated patients and severe rashes require discontinuation of the drug. There are no reports of outpatient desensitizations for delayed cutaneous reactions to lenalidomide. METHODS: Five patients presenting with delayed skin-limited hypersensitivity reactions to lenalidomide consistent with generalized maculopapular rashes, urticaria, and/or angioedema greater than 3-7 days after starting treatment were evaluated for desensitization. The protocol involved doubling doses with varying day intervals. The first dose was administered in the allergy clinic. The exclusion criteria for desensitization _ 2 of the following: 1) Unexplained fever 2) Mucosal or conjunctival were > involvement 3) Blistering rash 4) Persistent elevation of: absolute eosinophil count, liver enzymes, or other evidence of drug-induced end
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
organ damage. Once the patient reached the maintenance dose, lenalidomide was continued daily for prescribed course. RESULTS: None of the patients had sustained elevations of the laboratory values mentioned above during desensitization and did not have systemic signs or symptoms. All patients were able to reach maintenance doses. We followed the patients during their treatment period and there were no adverse side effects with the reintroduction of lenalidomide. CONCLUSIONS: The use of lenalidomide in refractory or relapsed multiple myeloma can be complicated by cutaneous hypersensitivity reaction. These delayed hypersensitivity reactions are amenable to outpatient desensitization as previously seen in desensitizations to oral allopurinol and sulfonamides.
953
An Atypical Case Of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) With Well-Formed NonNecrotizing Granulomas On Bone Marrow Biopsy Dr. Katie Miro, MD1, Dr. Eugenio Capitle, MD2; 1Rutgers- New Jersey Medical School, Newark, NJ, 2Rutgers-New Jersey Medical School, Newark, NJ. RATIONALE: DRESS is a severe drug reaction with multi-organ involvement, and numerous potential manifestations. We present an atypical case of DRESS with non-necrotizing granulomas on bone marrow biopsy. METHODS: We conducted a retrospective chart review of a case of DRESS. RESULTS: We present a 34 year old male with a history of new-onset seizure disorder, on phenytoin for a month, who was admitted to an outside hospital because of seizure, high fever, arthralgia, headache, and sore throat. During admission, he received numerous antimicrobials and had an extensive negative infectious evaluation including blood, urine, and cerebral spinal fluid cultures. Laboratory data demonstrated mild transaminitis, creatinine of 3.5 mg/dL, hemoglobin of 6.9 g/dL, and peak eosinophils of 2,000 or 10.6% (wbc518,600). A diffuse macular rash developed during admission. After 10 days, phenytoin and antimicrobials were stopped. He was transferred to our hospital after 17 days due to worsening status and unknown diagnosis. Echocardiogram, repeated due to dyspnea and tachycardia, demonstrated severe systolic dysfunction. Bone marrow biopsy, evaluating persistent anemia, revealed multiple wellformed non-necrotizing granulomas, mild eosinophilia, negative stains for acid-fast bacilli and fungus, and no hemophagocytosis. The allergy service evaluated and diagnosed him with DRESS from phenytoin. He received high dose prednisone and intravenous immunoglobulin with rapid improvement. After discharge, he continued to improve on a prolonged prednisone taper, although his systolic function remained decreased (EF525%). CONCLUSIONS: Our report illustrates the importance of recognizing all potential manifestations of DRESS, including non-necrotizing granulomas on bone marrow biopsy. Early recognition and treatment of DRESS may prevent end-organ damage.
951
Dual Hypersensitivity To Oxaliplatin Revealed Following Rapid Drug Desensitization: A History Of Anaphylaxis and New-Onset Hemolytic Anemia Dr. Jared Silver, MD, PhD1, Dr. Timothy Kyin, MD1, Dr. Mariana C. Castells, MD, PhD, FAAAAI2; 1Brigham and Women’s Hospital, Boston, MA, 2Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. RATIONALE: Oxaliplatin is a third generation platinum chemotherapy for colorectal cancer within FOLFOX regimens. After multiple exposures, hypersensitivity reactions are reported and some are IgE-mediated, including anaphylaxis. Co-existing type II hypersensitivity may also develop. METHODS: A 56yo male with metastatic colon cancer treated with FOLFOX manifested disease progression and with first re-exposure to oxaliplatin developed palmar erythema and with second re-exposure developed anaphylaxis (flushing, chest pressure, and dyspnea). Oxaliplatin skin testing was positive. The patient completed six oxaliplatin desensitizations using the BWH 3-bag 12-step protocol. Breakthrough reactions included fevers, chills, palmar erythema, back pain, and SOB. During the seventh desensitization, he presented with fever, rigors, palpitations, dizziness, and EKG changes. Desensitization was discontinued. RESULTS: EKGs demonstrated ST/T-wave abnormalities without troponin leak. Labs demonstrated 1.8 gm/dL decrease in hemoglobin (9.8 to 8.0 gm/dL, normal range 13.5-18), normal tryptase (5.6 ng/ml (reference range <11.5)), elevated total bilirubin (from 1.0 mg/dL to 3.1 (normal range 0-1)), elevated LDH (865 U/L (normal range 135-225)), reduced haptoglobin (<8mg/dL (normal range 30-200)), and positive direct Coombs testing. Platelets decreased by 117 K/ml to 142 (normal range 150-450). He was diagnosed with oxaliplatin-induced autoimmune hemolytic anemia. Oxaliplatin was discontinued. CONCLUSIONS: To our knowledge, this is the first reported case of a patient with type I hypersensitivity to oxaliplatin manifesting a type II hypersensitivity during chemotherapy desensitization. All desensitization providers should remain vigilant not only for direct drug toxicity and breakthrough type I hypersensitivity, but also for alternative forms of hypersensitivity which contraindicate agent-specific desensitization.
952
TUESDAY
Oupatient Lenalidomide Desensitization For Delayed Hypersensitivity Reactions In 5 Patients With Multiple Myeloma Dr. Min Jung Lee, MD1, Dr. Paige G. Wickner, MD2, Dr. Robert Schlossman, MD3, Dr. Paul Richardson, MD3, Dr. Jacob Laubach, MD3, Dr. Mariana C. Castells, MD, PhD, FAAAAI4; 1Brigham & Women’s Hospital, Boston, MA, 2Brigham & Women’s Hospital, Chestnut Hill, MA, 3Dana Farber Cancer Institute, Boston, MA, 4Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. RATIONALE: Lenalidomide is an immunomodulatory agent used in the treatment of multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Rash has been reported in nearly 30% of treated patients and severe rashes require discontinuation of the drug. There are no reports of outpatient desensitizations for delayed cutaneous reactions to lenalidomide. METHODS: Five patients presenting with delayed skin-limited hypersensitivity reactions to lenalidomide consistent with generalized maculopapular rashes, urticaria, and/or angioedema greater than 3-7 days after starting treatment were evaluated for desensitization. The protocol involved doubling doses with varying day intervals. The first dose was administered in the allergy clinic. The exclusion criteria for desensitization _ 2 of the following: 1) Unexplained fever 2) Mucosal or conjunctival were > involvement 3) Blistering rash 4) Persistent elevation of: absolute eosinophil count, liver enzymes, or other evidence of drug-induced end
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
organ damage. Once the patient reached the maintenance dose, lenalidomide was continued daily for prescribed course. RESULTS: None of the patients had sustained elevations of the laboratory values mentioned above during desensitization and did not have systemic signs or symptoms. All patients were able to reach maintenance doses. We followed the patients during their treatment period and there were no adverse side effects with the reintroduction of lenalidomide. CONCLUSIONS: The use of lenalidomide in refractory or relapsed multiple myeloma can be complicated by cutaneous hypersensitivity reaction. These delayed hypersensitivity reactions are amenable to outpatient desensitization as previously seen in desensitizations to oral allopurinol and sulfonamides.
953
An Atypical Case Of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) With Well-Formed NonNecrotizing Granulomas On Bone Marrow Biopsy Dr. Katie Miro, MD1, Dr. Eugenio Capitle, MD2; 1Rutgers- New Jersey Medical School, Newark, NJ, 2Rutgers-New Jersey Medical School, Newark, NJ. RATIONALE: DRESS is a severe drug reaction with multi-organ involvement, and numerous potential manifestations. We present an atypical case of DRESS with non-necrotizing granulomas on bone marrow biopsy. METHODS: We conducted a retrospective chart review of a case of DRESS. RESULTS: We present a 34 year old male with a history of new-onset seizure disorder, on phenytoin for a month, who was admitted to an outside hospital because of seizure, high fever, arthralgia, headache, and sore throat. During admission, he received numerous antimicrobials and had an extensive negative infectious evaluation including blood, urine, and cerebral spinal fluid cultures. Laboratory data demonstrated mild transaminitis, creatinine of 3.5 mg/dL, hemoglobin of 6.9 g/dL, and peak eosinophils of 2,000 or 10.6% (wbc518,600). A diffuse macular rash developed during admission. After 10 days, phenytoin and antimicrobials were stopped. He was transferred to our hospital after 17 days due to worsening status and unknown diagnosis. Echocardiogram, repeated due to dyspnea and tachycardia, demonstrated severe systolic dysfunction. Bone marrow biopsy, evaluating persistent anemia, revealed multiple wellformed non-necrotizing granulomas, mild eosinophilia, negative stains for acid-fast bacilli and fungus, and no hemophagocytosis. The allergy service evaluated and diagnosed him with DRESS from phenytoin. He received high dose prednisone and intravenous immunoglobulin with rapid improvement. After discharge, he continued to improve on a prolonged prednisone taper, although his systolic function remained decreased (EF525%). CONCLUSIONS: Our report illustrates the importance of recognizing all potential manifestations of DRESS, including non-necrotizing granulomas on bone marrow biopsy. Early recognition and treatment of DRESS may prevent end-organ damage.