The Therapeutic Approach for Relapsed CML - Episode 2

Treatment Approach for Relapsed CML

January 23, 2018

Javier A. Pinilla-Ibarz, MD, PhD:Today we are very fortunate to have several options for the treatment of newly diagnosed chronic phase chronic myeloid leukemia. There are 3 agents approved for frontline therapy. The first is imatinib, the second one is nilotinib, and the third one is dasatinib.

When we really discuss with our patient initial therapy for treatment of chronic phase chronic myeloid leukemia, it’s very important to really have the feedback of our patient in terms of dosing as well as to really take into consideration any potential comorbid condition the patient may experience or have experienced before as this may predispose them to have complications to specific drugs that we’re going to prescribe.

So, it’s important to take into consideration the past medical history of a patient who we really start therapy, or we need to decide to change therapy, with a tyrosine kinase inhibitor. In this case, the patient has a history of long QTC. There’s also history of current kidney disease, as well history of lung cancer treated with surgery, but also complicated by pleural effusion of thoracentesis. In this regard, all these comorbid conditions may really make us choose certain drugs or preferentially certain drugs versus others, at least considering that some of the drugs that we are currently use for the treatment of chronic myeloid leukemia may have complications such as pleural effusion and prolonged QTC, or even they may, in the long run in some cases, potentially decrease glomerular filtration.

The treatment of chronic myeloid leukemia in older patients is challenging and this is because of the multiple comorbid conditions that are very well studied, that most of the patients with CML are 60 to 65 years old presenting, as well as many, many times the polypharmacy that these patients are receiving. These are very, very important factors to consider at the time for which TKIs may be better tolerated, but also very important as predictors of potential side effects of each of the drugs that we are going to prescribe.

The patient on this case was treated with imatinib. Although we know that imatinib is a good frontline drug for the treatment of patients with chronic myeloid leukemia, we also know that the trial has been performed. And comparing imatinib with a second-generation TKI, one of the advantages to really treat patients with a high-risk Sokal score is that they have less progression during the first year and they achieve faster and deeper response. In this case, although no one can say that is contraindicated, the decision to really use a second-generation TKI should have be discussed with the patient because they may have some advantage in terms of better response during this first year.

In any patient who we decide to start treatment with a tyrosine kinase inhibitor, it is also important to take into consideration all these comorbid conditions. So, it’s very important to really control any abnormalities and any other comorbidities that can really increase the toxicity of the drugs that we’re going to prescribe. In this case, it’s important to really have a close collaboration with the primary physician, even with the cardiologist, to really work as a team and to try to avoid comorbid conditions that can affect the toxicity of the drugs that we’re going to prescribe.

Transcript edited for clarity.

A Patient With Relapsed CML and Comorbidities

December 2015

  • A 64-year-old male presented to his PCP with symptoms of fever, LUQ pain, and severe fatigue.
  • PMHx:
    • 2012: fainting associated with Long QT syndrome managed on propranolol.
    • 2014: stage 3 kidney disease (GFR; 45 mL/min)
    • 2014: NSCLC, stage IIA squamous histology treated with resection and chemoradiotherapy, pleural effusion managed with thoracentesis
  • PE: spleen palpable 1.5 inches below costal margin
  • CBC:
    • WBCs, 172,000/μL (metamyelocytes, 3%; myelocytes, 6%; basophils, 6%; blasts, 2%;
    • HCT, 30%
    • Platelets, 536,000/μL
    • Hb, 9.9 g/dL
  • Bone marrow biopsy: Ph+ in 20/20 metaphases
  • Q-PCR; BCR-ABL1/ABL1 ratio, 90%
  • The patient was started on therapy with imatinib 400 mg

  • March 2015:BCR-ABL1, 10% Q-PCR
  • June 2015:BCR-ABL1, 6% Q-PCR
  • September 2015:BCR-ABL1, 9% Q-PCR

December 2016:

  • BCR-ABL1, 15% Q-PCR
  • Bone marrow biopsy: Ph+ in 10/20 metaphases
  • Genetic testing was negative for known TKI resistance mutations
  • CBC normal count