Therapies for Chronic Myeloid Leukemia May Trigger PH Onset

Pulmonary hypertension (PH) may be triggered by therapies used in chronic myeloid leukemia (CML) treatment, namely the drugs Gleevec (imatinib), Tasigna (nilotinib), or Sprycel (dasatinib), according to a recent study.

The study, titled “Comparative Analysis Of Pulmonary Hypertension In Patients Treated With Imatinib, Nilotinib And Dasatinib,” was published in the journal Blood. 

Previous studies have reported that patients with CML treated with tyrosine kinase inhibitors (TKIs), namely Sprycel, may develop fatal PH. After discontinuing Sprycel, pulmonary hypertension symptoms improved in most patients, suggesting that perhaps only Sprycel triggered this condition.

Other studies, however, have suggested that other TKIs, such as Gleevec, can improve blood vessel resistance and PH symptoms in patients.

“To clarify the contradictory effects of TKIs, we used echocardiography to noninvasively screen CML patients who have been given imatinib, nilotinib or dasatinib,” researchers wrote. “We assessed the incidence of TKI-associated PH and subclinical PH, and analyzed the factors associated with onset of PH.”

The study enrolled 105 CML patients treated with Gleevec (37 patients), Tasigna (30), or Sprycel (38). Echocardiography allowed the assessment of triscupid regurgitation peak gradient (TRPG), an indicator of pulmonary arterial pressure (PAP). According to the criteria by the European Society of Cardiology, pulmonary hypertension is suspected when the TRPG is above 31 mmHg.

Results showed that the mean TRPG was 22.7 mmHg in the Gleevec group, 23.1 mmHg in the Tasigna group, and 23.4 mmHg for the Sprycel group. Although these values were not considered significantly different, they were higher than those in newly diagnosed CML patients not treated with TKIs (19 mmHg).

Importantly, nine out of the 105 patients had a TRPG above 31 mmHg, which signals PH development. Among the nine patients, one was treated with Gleevec, three were treated with Tasigna, and five received Sprycel.

Researchers also observed a tendency toward the association of TRPG with age or duration of TKI treatment.

Together, these results support that not only Sprycel, but also Gleevec and Tasigna, can be associated with the onset of subclinical pulmonary hypertension.

“Our study demonstrated high TRPG values in CML patients not only with dasatinib treatment but also with imatinib and nilotinib, suggesting that subclinical PH might be more common than expected in patients treated with any TKIs,” researchers wrote. “Careful screening with echocardiography is necessary, especially for older patients who have received TKIs for a long time.”