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More on Imatinib for ALL in the Elderly
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: Treatment of acute lymphoblastic leukemia in elderly patients remains problematic. Recent data suggests imatinib with chemotherapy is both effective and well-tolerated in elderly patients with Philadelphia chromosome-positive ALL. In the current Italian trial, imatinib and prednisone, but without additional chemotherapy, used as initial therapy, produced complete hematological remission in all 29 elderly patients treated. Treatment was oral, conducted as an out patient and well tolerated.
Source: Vignetti M, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell 'Adulto (GIMEMA) LA 0201-B protocol. Blood. 2007;109:3676-3678.
Approximately 1/3 of adult acute lymphoblastic leukemia is Philadelphia chromosome positive1,2 and this percentage may be even higher in the elderly3 in whom it is considered a negative prognostic factor.4 Recently, a consortium of French and Belgian investigators reported the value of imatinib used with additional chemotherapy in elderly ALL patients as consolidation therapy. In that trial, at the end of one year, relapse-free survival was 58%, which compared favorably with 11% of the historic controls treated similarly but without added imatinib.5 The current report from the Gruppo Italiano Malattie Ematologiche dell 'Adulto (GIMEMA) details their experience with imatinib as initial therapy with prednisone but without additional chemotherapy.
Thirty older adult patients (> 60 years) with Ph+ ALL received prednisone (starting at 10 mg/m2 but increased to 40 mg/m2 for at least 45 days) and imatinib 800 mg/daily. The imatinib was started after one week of prednisone alone. Twenty-nine patients were evaluable for response and all of them obtained a hematological complete remission. No major toxicity was observed and for most, treatment was conducted out patient. During the 45 day induction period, only 7 patients (23%) experienced either a dose reduction or a temporary discontinuation of imatinib due to extrahematologic toxicities. Median survival from diagnosis was 20 months (95% confidence interval [CI]: 12-not reached) and the median duration of hematological remission was 8 months (95% CI: 4-27 months). Of the 29 patients, 14 relapsed after a median time of 4 months (range, 3-28 months), 2 patients died in CR at 5 and 15 months, and 13 patients remained alive in continuous remission after a median time of 10 months from response (range 1-32 months). The probability of overall survival and disease free survival at 12 months was 74% (95%CI: 54-94%) and 48% (95% CI: 28-69%).
ALL, and in particular Ph+ ALL occurring in older adults has remained a challenge, primarily because the intensive cytotoxic chemotherapy regimens required to induce remission is fraught with toxicity in this age group. However, recent studies have indicated that imatinib when used with steroid and chemotherapy as either consolidation5 or initial induction therapy6 improves outcomes and with minimal added toxicity. The current report takes this one step further. Imatinib used with prednisone but without additional chemotherapy was shown to induce remissions and result in survival figures comparable, if not superior to conventional chemotherapy, and with manageable toxicity. Furthermore, the great majority of management was out patient, considered a definite advantage in this setting.
Thus, for newly diagnosed Ph+ ALL in older adults, imatinib alone offers an effective and well tolerated treatment choice. However, although remissions were common, they were of relatively short duration for approximately 50%. Further research may identify additional well tolerated agents (eg, vincristine) which when added, either as consolidation or during induction therapy, could improve overall remission duration and survival.
1. Bloomfield CD, et al. Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia. Blood. 1986;67:415-420.
2. Kurzrock R, et al. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988;319:990-998.
3. Annino L, et al. Acute lymphoblastic leukemia in the elderly. Hematol J. 2002;3:219-223.
4. Delannoy A, et al. Treatment of acute lymphoblastic leukemia in the elderly: an evaluation of interferon alpha given as a single agent after complete remission. Leuk Lymphoma. 2002;43:75-81.
5. Delannoy A, et al. Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study. Leukemia. 2006;20:1526-1532.
6. Ottmann OG, et al. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Cancer. 2007;109:2068-2076.