Non-Hodgkin Lymphoma Elevated in Imatinib-Treated CML Survivors

A new study found no significantly increased incidence of secondary malignancies in patients with chronic myeloid leukemia (CML) treated with imatinib. There was, however, an increased incidence specifically of non-Hodgkin lymphoma (NHL) among these patients.

The treatment of CML with tyrosine kinase inhibitors (TKIs) has dramatically increased the life span of most patients, with an 8-year survival rate of about 88%. With longer survival, there is concern over secondary malignancies, though in CML the data have been conflicting on the risks.

Some previous research has suggested that TKIs themselves could play a role in secondary malignancies. “Preclinical data demonstrated an interaction of imatinib with DNA repair mechanisms,” wrote study authors led by Susanne Saussele, MD, of Heidelberg University in Germany. “In studies with rats, neoplastic changes occurred in kidneys, urinary bladder, urethra, preputial and clitoral glands, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach.”

The authors analyzed data from 1,525 patients included in the CML Study IV, with a median follow-up of 67.5 months. The results were published in Leukemia.

In total, there were 67 secondary malignancies in 64 patients; 26 of these patients (41%) were female. The median time from CML diagnosis to diagnosis of secondary malignancy was 2.4 years. The CML Study IV had five treatment arms comparing various imatinib doses in combination with interferon-alpha or cytarabine; the secondary malignancy rate was not significantly different across these treatment arms.

Twelve patients who had a primary cancer before the CML diagnosis developed another malignancy while on TKI therapy. Three patients developed more than one secondary malignancy.

There was a range of secondary malignancy types: 13% were prostate cancer, 10% were NHL, 9% were colorectal cancer (CRC), 9% were lung cancer, and others were less frequent. The overall standardized incidence ratio (SIR) for all malignancies except non-melanoma skin cancer, in comparison to the German general population, was 0.88 (95% CI, 0.63–1.20) in men and 1.06 (95% CI, 0.69–1.55) in women.

These similarities to the general population were not the same, however, when looking at specific types of malignancy. The SIRs ranged from a low of 0.49 for CRC in men to a high of 3.33 for kidney cancer in women. Only one malignancy’s SIR reached statistical significance: the SIR for NHL in men was 3.33 (95% CI, 1.06–8.04), and in women it was 4.29 (95% CI, 1.09–11.66).

“Overall, our data do not support an increased risk for secondary malignancies in CML patients treated with imatinib, as the SIR of men and women were similar to that of the general population,” the authors wrote. The increase in NHL, however, is notable, though they pointed out that three of the cases were low-grade lymphomas that are easily missed in the general population but found in a strictly monitored study cohort. “Ideally, long-term follow-up on large cohorts of CML patients under treatment is warranted,” they concluded.