Just Accepted by Leukemia & Lymphoma
Musculoskeletal pain may be associated with imatinib withdrawal syndrome in chronic myeloid leukemia patients Yoshimi Ishii, Maki Hagihara, Ai Kato, Taiki Ando, Megumi Itabashi, Satoshi Koyama, Wataru Yamamoto, Kenji Motohashi, Kenji Matsumoto, Shin Fujisawa
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
DOI: 10.3109/10428194.2015.1064531
© 2015 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
Musculoskeletal pain may be associated with imatinib withdrawal syndrome in chronic myeloid leukemia patients
Yoshimi Ishii, Maki Hagihara, Ai Kato, Taiki Ando, Megumi Itabashi, Satoshi Koyama,
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
Wataru Yamamoto, Kenji Motohashi, Kenji Matsumoto, Shin Fujisawa
Department of Hematology, Yokohama City University Medical Center, 4-57,
Urafune-cho, Minami-ku, Yokohama 232-0024, Japan
Correspondence: Dr. Yoshimi Ishii, Department of Hematology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024, Japan, Phone: +81-45-261-5656, Fax: +81-45-241-2812, E-mail: [email protected]
Short title: Musculoskeletal pain is imatinib withdrawal
Keywords: chronic myeloid leukemia, stop imatinib, withdrawal, musculoskeletal pain
1
Letters to the Editor Chronic myeloid leukemia (CML) is caused by the active BCR-ABL tyrosine kinase resulting from the t(9;22)(q34;q11.2) translocation [1]. Imatinib is a BCR-ABL inhibitor that dramatically improved prognosis in patients with chronic-phase CML [2]. Recently, Rousselot et al. reported that losing the major molecular response (MMR) after imatinib discontinuation is estimated to be 35% at 12 months and 36% at 24 months in the Stop Imatinib study (A-STIM) [3]; the overall probability of maintaining the complete molecular response (CMR) in patients with stable confirmed CMR (cCMR) and undetectable cCMR before the study was
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
estimated at 55% and 43%, respectively. It is probable that imatinib can be safely withdrawn. However, the adverse effect of discontinuation of imatinib is still unknown. Richter et al. reported that musculoskeletal pain in patients with CML after discontinuation of imatinib is probably associated with withdrawal syndrome [4]. Here, we report five cases in which the patients developed musculoskeletal pain after stopping imatinib. Between February 2014 and March 2015, 13 patients who maintained CMR for at least two years were discontinued from using imatinib at Yokohama City University Medical Center. Of the 13 patients, five patients developed musculoskeletal pain with a median onset of three months after stopping imatinib. Patient characteristics are summarized in Table I. The patients consisted of three men and two women with a median age of 64 years (range, 51-73 years). They achieved MMR and CMR with median times of 9 months (range, 6-18 months) and 9 months (range, 6-38 months), respectively. The median years from initiation to discontinuation of imatinib were 97 months (range, 82-107 months). They maintained CMR for a median of 80 months (range, 34-97 months). The pain was localized to various parts of the body, especially the limbs and shoulders. C-reactive protein (CRP) was elevated in four patients. Creatine kinase (CK) was elevated in one patient. Orthopedic diseases such as rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) were suspected, and the patients were examined by an orthopedist. One patient was examined by a rheumatologist. However, the cause of musculoskeletal pain was unknown. The symptoms were grades 1-2 according to the Common Terminology Criteria for Adverse Event Scale (version 4.0). Non-steroidal anti-inflammatory drugs and a poultice were administered for four patients. Clinical symptoms improved gradually in four patients with a median time of 5 months (range, 2-7 months), but not in one of the patients. They did not need steroids. One patient lost CMR
2
(maintained MMR) nine months after discontinuation of imatinib, and dasatinib treatment was initiated. Richter et al. described that, of 50 patients who stopped imatinib, 15 (30%) developed musculoskeletal pain. Of the current five patients, four developed musculoskeletal pain during imatinib therapy; of eight patients who did not develop symptoms after stopping imatinib, three experienced symptoms during imatinib therapy. None of the 13 patients developed additional symptoms after stopping imatinib. Musculoskeletal pain with imatinib administration is well known, but musculoskeletal pain after stopping imatinib has not been
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
well described. Symptoms of the current five patients were very similar, thus it is possible that the symptoms were associated with imatinib withdrawal. The mechanism of withdrawal syndrome should be further investigated. Recently, following the A-STIM study, stoppage of imatinib therapy has increased, thus physicians should be aware of development of possible withdrawal syndrome after imatinib withdrawal.
3
References [1] Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164-172. [2] Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009; 27: 6041-6051. [3] Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
Oncol 2014; 32: 424-430. [4] Richter J, Söderlund S, Lübking A, et al. Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J Clin Oncol 2014; 32: 2821-2823.
4
Musculoskeletal pain may be associated with imatinib withdrawal syndrome in chronic myeloid leukemia patients Yoshimi Ishii, Maki Hagihara, Ai Kato, Taiki Ando, Megumi Itabashi, Satoshi Koyama, Wataru Yamamoto, Kenji Motohashi, Kenji Matsumoto, Shin Fujisawa
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
DOI: 10.3109/10428194.2015.1064531
© 2015 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
Musculoskeletal pain may be associated with imatinib withdrawal syndrome in chronic myeloid leukemia patients
Yoshimi Ishii, Maki Hagihara, Ai Kato, Taiki Ando, Megumi Itabashi, Satoshi Koyama,
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
Wataru Yamamoto, Kenji Motohashi, Kenji Matsumoto, Shin Fujisawa
Department of Hematology, Yokohama City University Medical Center, 4-57,
Urafune-cho, Minami-ku, Yokohama 232-0024, Japan
Correspondence: Dr. Yoshimi Ishii, Department of Hematology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024, Japan, Phone: +81-45-261-5656, Fax: +81-45-241-2812, E-mail: [email protected]
Short title: Musculoskeletal pain is imatinib withdrawal
Keywords: chronic myeloid leukemia, stop imatinib, withdrawal, musculoskeletal pain
1
Letters to the Editor Chronic myeloid leukemia (CML) is caused by the active BCR-ABL tyrosine kinase resulting from the t(9;22)(q34;q11.2) translocation [1]. Imatinib is a BCR-ABL inhibitor that dramatically improved prognosis in patients with chronic-phase CML [2]. Recently, Rousselot et al. reported that losing the major molecular response (MMR) after imatinib discontinuation is estimated to be 35% at 12 months and 36% at 24 months in the Stop Imatinib study (A-STIM) [3]; the overall probability of maintaining the complete molecular response (CMR) in patients with stable confirmed CMR (cCMR) and undetectable cCMR before the study was
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
estimated at 55% and 43%, respectively. It is probable that imatinib can be safely withdrawn. However, the adverse effect of discontinuation of imatinib is still unknown. Richter et al. reported that musculoskeletal pain in patients with CML after discontinuation of imatinib is probably associated with withdrawal syndrome [4]. Here, we report five cases in which the patients developed musculoskeletal pain after stopping imatinib. Between February 2014 and March 2015, 13 patients who maintained CMR for at least two years were discontinued from using imatinib at Yokohama City University Medical Center. Of the 13 patients, five patients developed musculoskeletal pain with a median onset of three months after stopping imatinib. Patient characteristics are summarized in Table I. The patients consisted of three men and two women with a median age of 64 years (range, 51-73 years). They achieved MMR and CMR with median times of 9 months (range, 6-18 months) and 9 months (range, 6-38 months), respectively. The median years from initiation to discontinuation of imatinib were 97 months (range, 82-107 months). They maintained CMR for a median of 80 months (range, 34-97 months). The pain was localized to various parts of the body, especially the limbs and shoulders. C-reactive protein (CRP) was elevated in four patients. Creatine kinase (CK) was elevated in one patient. Orthopedic diseases such as rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) were suspected, and the patients were examined by an orthopedist. One patient was examined by a rheumatologist. However, the cause of musculoskeletal pain was unknown. The symptoms were grades 1-2 according to the Common Terminology Criteria for Adverse Event Scale (version 4.0). Non-steroidal anti-inflammatory drugs and a poultice were administered for four patients. Clinical symptoms improved gradually in four patients with a median time of 5 months (range, 2-7 months), but not in one of the patients. They did not need steroids. One patient lost CMR
2
(maintained MMR) nine months after discontinuation of imatinib, and dasatinib treatment was initiated. Richter et al. described that, of 50 patients who stopped imatinib, 15 (30%) developed musculoskeletal pain. Of the current five patients, four developed musculoskeletal pain during imatinib therapy; of eight patients who did not develop symptoms after stopping imatinib, three experienced symptoms during imatinib therapy. None of the 13 patients developed additional symptoms after stopping imatinib. Musculoskeletal pain with imatinib administration is well known, but musculoskeletal pain after stopping imatinib has not been
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
well described. Symptoms of the current five patients were very similar, thus it is possible that the symptoms were associated with imatinib withdrawal. The mechanism of withdrawal syndrome should be further investigated. Recently, following the A-STIM study, stoppage of imatinib therapy has increased, thus physicians should be aware of development of possible withdrawal syndrome after imatinib withdrawal.
3
References [1] Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164-172. [2] Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009; 27: 6041-6051. [3] Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin
Leuk Lymphoma Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/01/15 For personal use only.
Oncol 2014; 32: 424-430. [4] Richter J, Söderlund S, Lübking A, et al. Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J Clin Oncol 2014; 32: 2821-2823.
4
