Managing Myelodysplastic Syndromes

Mr. CH is a 71-year-old retired naval officer who works full time as an aerospace engineer. He began experiencing increasing lethargy and malaise in August 2000 at the age of 65. He was finding it difficult to concentrate and became tired by the end of the day. An evaluation by his primary care physician revealed anemia and iron deficiency. CH received a trial of iron and erythropoietin with no substantial improvement. His anemia progressed; he required his first red blood cell transfusion in September 2001. He was referred to a hematologist at a regional comprehensive cancer center.

As a part of his evaluation he had a bone marrow biopsy, aspirate, and cytogenetics, which revealed myelodysplastic syndromes (MDS), refractory anemia, cellularity of 20%, 2% blasts, with anemia (hemoglobin 8.8 g/dL, MCV 119), and leukopenia (WBC 2,000, neutrophils 61%). Cytogenetics confirmed the presence of a solitary cytogenetic abnormality, deletion 5 q, a favorable prognostic finding in MDS. The final IPSS (International Prostate Symptom Score) was zero, indicating low-risk disease. No FDA-approved therapies were available in 2001 and the patient was enrolled in a clinical trial with a matrix metalloproteinase inhibitor, prinomastat. His transfusion requirements did not improve and he experienced treatment-related severe joint pain. He modified his work schedule to limit travel and had considered retirement due to his symptoms and concern that no treatment would be effective. Transfusion support was continued with increasing frequency.

Treatment summary

The patient remained motivated to continue treatment. On April 2, 2002, CH began a new clinical trial with lenalidomide, an oral immunomodulatory agent. Prior to starting this trial he had received a total of 12 units of packed red blood cells (PRBCs), had a white blood cell (WBC) count of 2,700 (absolute neutrophil count [ANC] 1,758), and platelets of 197,000. The initial dose on the trial was 25 mg given once daily. Weekly blood counts were obtained and within 3 weeks he developed significant cytopenias (WBC 1,000, ANC 140, platelets 38,000, and hemoglobin 8.5 g/dL).

The drug was held and he received a PRBC transfusion on April 22, 2002. He remained afebrile and showed no evidence of bleeding. The cytopenias resolved within 2 weeks of holding the drug without intervention. More importantly, during the drug holiday the hemoglobin rose independent of transfusion by 1 g/dL. Within 4 weeks of holding the drug, the blood counts showed further hematological improvement and a continued Hgb response (WBC 2600, ANC 1300, Hgb 10.3, platelets 58,000). Treatment was resumed at a dose of 10 mg daily using a schedule of 3 weeks on and 1 week off. CH has continued on the drug with further dose reduction required to 5 mg daily, three weeks on and one week off. He has received three injections of pegfilgrastim (Neulasta) for an ANC < 500 and concurrent sinusitis. See Table 1 for a summary of his findings.

CH continues to have moderate but asymptomatic thrombocytopenia, which has not required intervention. He has remained transfusion independent for 4 ½ years and continues to work full time at the age of 71. A repeat bone marrow biopsy, aspirate, and cytogenetics 3 months after initiating therapy showed no evidence of the 5q- abnormality, indicating some effect on the underlying disease. He did experience mild pruritus, but no other nonhematologic toxicities.

CH has been able to resume travel and has joined a fitness program and is working out three times a week. CH is an enthusiastic clinical trial participant and continues to chart his progress noting fluctuations from visit to visit, but an overall positive trend in his blood counts.

Clinical Trial Overview

CH was one of 43 evaluable patients participating in the initial trial using lenalidomide. 63% of the patients achieved transfusion independence, and cytogenetic responses were documented in 55% of the patients. Cytogenetic remission was documented in 75% of a subset of patient with the 5q- abnormality.[1] These have been documented rarely in therapies for MDS. Based on the initial clinical trial, a phase II multicenter trial was conducted, providing additional evidence of response and safety information. The drug was approved on December 27, 2005, for treatment of transfusion-dependent MDS with the 5q- cytogenetic abnormality with or without additional cytogenetic abnormalities.

The most common toxicity is myelosuppression. The initial recommended dose is 10 mg daily. Weekly blood counts are recommended for the first 8 weeks, with dose modification guidelines provided by the manufacturer. Management of myelosuppression is the primary nursing consideration. Moderate but asymptomatic cytopenias most often require no intervention. Patients should be provided with clear guidelines on infection and bleeding precautions and reportable signs and symptoms that require immediate intervention. Although teratogenicity has not been reported in animal studies, the drug is a thalidomide analog and to ensure safety it is prescribed under the RevAssist program.[2]

Conclusions

This case study illustrates the benefit of clinical trial participation in diseases with limited available treatment options and evolving scientific discoveries. Myelodysplastic syndrome is one of many diagnoses with a rapidly changing treatment paradigm based on scientific advances and clinical management strategies. The oncology nursing professional is critical to documenting adverse events and providing safe clinical management and patient support. The goals of therapy in the patient with MDS are to improve quality of life, minimize toxicity, improve hematopoiesis and reduce cytopenias, and prolong survival. These outcomes have been effectively demonstrated in the treatment of this patient. In addition, there is evidence of cytogenetic remission, indicating some effect on the underlying disease. Consideration of the unique needs of the elderly patient are critical to optimal clinical management and quality of life, however advanced age alone should not exclude the older patient from active therapies as illustrated in the case study.

Disclosures:

The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. List A, Kurtin S, Roe DJ, et al: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352:549-557, 2005.

2. Revlimid (lenalidomide) prescribing information (www.revlimid.com).