Imatinib appears safe, effective for the long haul

CHICAGO – After a decade on therapy with imatinib, a majority of patients with chronic myeloid leukemia will experience an adverse drug reaction, but most reactions are mild and manageable, according to results from a study presented at the annual meeting of the American Society of Clinical Oncology.

Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy at some point, 1,018 (74%) had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities, and there were no deaths attributed to imatinib, reported Dr. Rüdiger Hehlmann of the University of Heidelberg, Germany, and his colleagues.

Adverse drug reactions were manageable even when imatinib was combined with interferon-alfa (IFN-alfa), the investigators from the German CML Study Group reported in a poster at the meeting.

"After 10 years, imatinib continues to be an excellent choice for most patients with CML," they wrote.

In the 13 years that have elapsed since imatinib was approved in the United States as the first-in-class tyrosine kinase inhibitor, second-generation TKIs and other targeted agents have emerged, drawing attention to the safety of the older regimen.

The investigators evaluated long-term follow-up data and analyzed adverse drug reaction data for 1,501 patients treated with imatinib monotherapy in doses of 400 or 800 mg/day, as well as imatinib 400 mg in combination with IFN-alfa.

At the most recent evaluation, in November 2013, 164 patients had died, 1,003 were still on imatinib, 275 had been switched to a second-generation TKI, and 106 underwent bone marrow transplant (some patients received more than one therapy, accounting for the difference in total numbers).

The median follow-up time was 6.5 years, with some patients on study for as long as 11.5 years.

The probability of 10-year survival was 84%, and of 10-year progression-free survival was 81%.

An analysis of survival by molecular response rates showed an overall survival rate of 89% for those who achieved a major molecular response (MR, defined as a BCR-ABL RNA level of 0.1% or less), and 74% for those who achieved MR 4.5 (a 4.5 log₁₀reduction or greater in BCR-ABL transcripts).

The 8-year probabilities for all grades of adverse events among the patients who received imatinib monotherapy were 41% for edema or fluid overload, 38% for gastrointestinal toxicities, 25% for myalgia/arthralgia, 20% for rash, 17% for musculoskeletal events, 17% for fatigue, 11% for neurological toxicities, and 10% for flulike symptoms.

Five patients had grade 2 or 3 peripheral arterial occlusive disease, but it was not clear whether these events were associated with imatinib.

For most patients the first adverse drug reaction occurred within 3 years of starting on imatinib, with the frequency of reactions decreasing thereafter.

Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.

CHICAGO – After a decade on therapy with imatinib, a majority of patients with chronic myeloid leukemia will experience an adverse drug reaction, but most reactions are mild and manageable, according to results from a study presented at the annual meeting of the American Society of Clinical Oncology.

Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy at some point, 1,018 (74%) had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities, and there were no deaths attributed to imatinib, reported Dr. Rüdiger Hehlmann of the University of Heidelberg, Germany, and his colleagues.

Adverse drug reactions were manageable even when imatinib was combined with interferon-alfa (IFN-alfa), the investigators from the German CML Study Group reported in a poster at the meeting.

"After 10 years, imatinib continues to be an excellent choice for most patients with CML," they wrote.

In the 13 years that have elapsed since imatinib was approved in the United States as the first-in-class tyrosine kinase inhibitor, second-generation TKIs and other targeted agents have emerged, drawing attention to the safety of the older regimen.

The investigators evaluated long-term follow-up data and analyzed adverse drug reaction data for 1,501 patients treated with imatinib monotherapy in doses of 400 or 800 mg/day, as well as imatinib 400 mg in combination with IFN-alfa.

At the most recent evaluation, in November 2013, 164 patients had died, 1,003 were still on imatinib, 275 had been switched to a second-generation TKI, and 106 underwent bone marrow transplant (some patients received more than one therapy, accounting for the difference in total numbers).

The median follow-up time was 6.5 years, with some patients on study for as long as 11.5 years.

The probability of 10-year survival was 84%, and of 10-year progression-free survival was 81%.

An analysis of survival by molecular response rates showed an overall survival rate of 89% for those who achieved a major molecular response (MR, defined as a BCR-ABL RNA level of 0.1% or less), and 74% for those who achieved MR 4.5 (a 4.5 log₁₀reduction or greater in BCR-ABL transcripts).

The 8-year probabilities for all grades of adverse events among the patients who received imatinib monotherapy were 41% for edema or fluid overload, 38% for gastrointestinal toxicities, 25% for myalgia/arthralgia, 20% for rash, 17% for musculoskeletal events, 17% for fatigue, 11% for neurological toxicities, and 10% for flulike symptoms.

Five patients had grade 2 or 3 peripheral arterial occlusive disease, but it was not clear whether these events were associated with imatinib.

For most patients the first adverse drug reaction occurred within 3 years of starting on imatinib, with the frequency of reactions decreasing thereafter.

Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.

CHICAGO – After a decade on therapy with imatinib, a majority of patients with chronic myeloid leukemia will experience an adverse drug reaction, but most reactions are mild and manageable, according to results from a study presented at the annual meeting of the American Society of Clinical Oncology.

Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy at some point, 1,018 (74%) had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities, and there were no deaths attributed to imatinib, reported Dr. Rüdiger Hehlmann of the University of Heidelberg, Germany, and his colleagues.

Adverse drug reactions were manageable even when imatinib was combined with interferon-alfa (IFN-alfa), the investigators from the German CML Study Group reported in a poster at the meeting.

"After 10 years, imatinib continues to be an excellent choice for most patients with CML," they wrote.

In the 13 years that have elapsed since imatinib was approved in the United States as the first-in-class tyrosine kinase inhibitor, second-generation TKIs and other targeted agents have emerged, drawing attention to the safety of the older regimen.

The investigators evaluated long-term follow-up data and analyzed adverse drug reaction data for 1,501 patients treated with imatinib monotherapy in doses of 400 or 800 mg/day, as well as imatinib 400 mg in combination with IFN-alfa.

At the most recent evaluation, in November 2013, 164 patients had died, 1,003 were still on imatinib, 275 had been switched to a second-generation TKI, and 106 underwent bone marrow transplant (some patients received more than one therapy, accounting for the difference in total numbers).

The median follow-up time was 6.5 years, with some patients on study for as long as 11.5 years.

The probability of 10-year survival was 84%, and of 10-year progression-free survival was 81%.

An analysis of survival by molecular response rates showed an overall survival rate of 89% for those who achieved a major molecular response (MR, defined as a BCR-ABL RNA level of 0.1% or less), and 74% for those who achieved MR 4.5 (a 4.5 log₁₀reduction or greater in BCR-ABL transcripts).

The 8-year probabilities for all grades of adverse events among the patients who received imatinib monotherapy were 41% for edema or fluid overload, 38% for gastrointestinal toxicities, 25% for myalgia/arthralgia, 20% for rash, 17% for musculoskeletal events, 17% for fatigue, 11% for neurological toxicities, and 10% for flulike symptoms.

Five patients had grade 2 or 3 peripheral arterial occlusive disease, but it was not clear whether these events were associated with imatinib.

For most patients the first adverse drug reaction occurred within 3 years of starting on imatinib, with the frequency of reactions decreasing thereafter.

Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.