Acute Myeloid Leukemia with Myelodysplastic-Related Cytogenetics - Episode 4

Consolidation Chemotherapy in AML

July 23, 2019

James K. McCloskey II, MD:After our patient has achieved a remission, I think the next question is always what do we do next? Typically, in a patient who received intensive induction chemotherapy, we would proceed with chemotherapy-based consolidation. The question becomes in an older patient, how well are they going to tolerate continued cycles of chemotherapy, and what’s the added benefit?

In patients who receive Vyxeos [liposomal cytarabine/daunorubicin], we have looked at the outcomes of patients who had a CR [complete remission] and then proceeded with consolidation therapy. I think one important note would be that these data are obtained by post hoc analysis, so it wasn’t a prespecified patient population. But if we look at patients who achieved a remission and either got Vyxeos versus 5+2 [cytarabine/daunorubicin] in the clinical trial, the outcome for patients with Vyxeos was substantially better.

Patients treated with Vyxeos in CR1 [first complete remission] or CRi [complete remission with incomplete hematologic recovery] with consolidation with Vyxeos, had an improved overall survival of 25 months compared to only 8.5 months in patients who received 5+2 consolidation.

Whenever we consider induction chemotherapy for an older patient, potentially a more frail patient population, one of our main concerns is always the toxicity of the regimen. In fact, historically this has been one of the most important limiting factors in our ability to treat older patients. Understandably, there was a lot of concern about the potential increased toxicity of Vyxeos or even induction in this more frail elderly patient population. But I think if you look at the breakdown, we really didn’t see a lot of new toxicities. In fact, the most common toxicities were ones that we’d except with any induction regimen.

When you look at the nuances of the breakdown, there was a slight increased risk of hemorrhage in the patients treated with Vyxeos. I think that’s important especially when we think about treating these patients in the outpatient setting. We want to remember that there is increased myelosuppression with Vyxeos, and there could be a delayed time to count recovery. If we see patients beginning to recover their neutrophil count, we need to remember that they should come back regularly for count checks and platelet transfusions so that we maintain the platelet count in a safe range to avoid hemorrhagic complications.

The other nuance is that if you look at the GI [gastrointestinal] toxicity profile between Vyxeos and 7+3 [cytarabine/daunorubicin], there were slightly fewer GI toxicities with the Vyxeos compared to the 7+3 arm—that included things like colitis, mucositis, and diarrhea. These seemed to be slightly less significant in the Vyxeos arm than the patients who received 7+3.

Transcript edited for clarity.

Case: A 68-Year-Old Man Withde novoAML

History and Physical:

  • A 68-year-old man presented with significant fatigue and shortness of breath on exertion; reports low-grade fever for the past few days.
  • PMH: mild hypertension, hypercholesterolemia, both medically managed; no history of malignancy

Laboratory work-up:

  • WBC, 2.6 X 109/L
  • ANC, 1.2 X 109/L
  • Hb, 9.4 X 109/L
  • Hct, 32%
  • RBC, 3.3 X 109/L
  • MCV, 121 fL
  • PLT, 95 X 109/L

Bone marrow biopsy:65% blasts

Peripheral blood smear;70% blasts

FISH;del(5q), del (20q)

Diagnosis;AML, myelodysplasia-related cytogenetic abnormalities