Rapidly Progressing Acute Myeloid Leukemia - Episode 1

Case-Based Overview: Newly Diagnosed Acute Myeloid Leukemia

Naval G. Daver, MD:This is the case of a 64-year-old patient with newly diagnosed acute myeloid leukemia. The patient has significant comorbidities, including an elevated BMI [body mass index], signifying a significant obesity, as well as underlying pneumonia and prior history of high blood pressure and diabetes. These are all comorbidities that make us start thinking about the optimal therapeutic choice for this patient. It’s also very important to confirm the diagnosis for this patient, and the bone marrow that has been done does show a diagnosis of acute myeloid leukemia with more than 20% blast, which meets the WHO [World Health Organization] criteria.

The main things that I’m thinking about at this time for this patient are, number 1, stabilizing him. The CT [computed tomography] scan does show that he has an active infiltrate concerning for an infectious pneumonia. So, I would probably start the patient on some oral or IV [intravenous] antibiotics, depending on his clinical signs and symptoms. And then most importantly, try to rush the molecular and chromosome testing to try and identify the optimal frontline therapy.

At this time, I’m probably not inclined to go with intensive induction therapy for this patient. This is not just because of his age—he is 64, which is still a patient that could be eligible for intensive induction with cytarabine, anthracycline—but more so because of his significant comorbidities: the elevated BMI, the ongoing pneumonia, the blood pressure and diabetes issues. I’m thinking of going with lower intensity therapies such as hypomethylating agent or low-dose cytarabine with venetoclax, or potentially targeted therapy-based combinations if we find a targetable mutation such asFLT3orIDH1,IDH2mutations.

Historically for such a patient we would have considered standard induction therapy, which is a combination of cytarabine anthracycline. There are many different ways this induction therapy can be given. The most common is what we call “3 plus 7,” which is 3 days of the anthracycline—either idarubicin or daunorubicin—and 7 days of the cytarabine, either 100 or 200 per meter square. There are variations, some of which have shown higher response rates, such as FLAG-IDA [fludarabine, cytarabine, idarubicin and filgrastim], CLIA [idarubicin plus high‐dose cytarabine + clofarabine/cladribine], and others. So that would probably be the standard therapy that we’ve used for acute myeloid leukemia for about 40 years now.

If this patient was diagnosed 4 or 5 years ago, for example, that would be the most likely treatment approach. We also did have lower intensity therapies such as Vidaza [azacitidine], decitabine. These have been available now for the last 12 or 13 years. The problem was that the response rates with Vidaza or decitabine as single-agent were only about 20% to 28%, which is much lower than the 65% to 75% you could get with 7 + 3. In most patients we would try to push to give them 7 + 3 unless, of course, they were extremely sick in the ICU [intensive care unit] or had really severe comorbidities.

But now with the advent of the new combinations such as azacitidine or decitabine with venetoclax added, we’re seeing the response rates are going up to about 70% to 75%. Now, we actually don’t necessarily push for the traditional 7 + 3 induction if we feel that the patient may not tolerate it but go for the azacitidine with venetoclax type of approach instead.

Transcript edited for clarity.


Case: A Male With Rapidly Progressing Acute Myeloid Leukemia

A 64-year-old male presented with a 2-week history of subjective fever, fatigue, shortness of breath, dizziness, and cough

H & P

  • PE: Temperature 99.1oF, pallor of the conjunctiva, multiple ecchymosis on upper and lower extremities
  • PMH: DM controlled on metformin, hypertension, BMI >35, recent history of pneumonia treated with oral antibiotics
  • ECOG: 2

Diagnostic Work- Up

  • Initial pertinent positive lab values:
    • WBC: 2.3 x 103/µL, RBC: 3.1212 x 106/µL, Hb: 9.3 g/dL, Ht: 23.1%, Plt: 83 x 103/µL, LDH: 275 U/L, blasts: 36%, absolute neutrophil count: 320 cells/µL, PT: 16.1s,
    • Few auer rods noted on bone marrow aspiration
  • Diagnosed with AML with 43% blasts on pathology evaluation, flow-cytometry confirms AML
  • Molecular panel and cytogenic testing pending and RUSH requested
  • Chest CT revealed patchy consolidation in the left lower lung lobe with ill-defined nodules
  • EKG and Echocardiogram unremarkable
  • Started on prophylactic voriconazole, cefpodoxime, and valacyclovir

Treatment

  • Patient was started at this time on azacitidine and venetoclax; Azacitidine 75mg/m2Days 1-7 and Venetoclax Days 1-28. Venetoclax dose was 100mg with voriconazole.
  • Was admitted for tumor lysis monitoring and hydration. Tolerated cycle 1 well. continue until disease progression or unacceptable toxicity
  • Day 28 post-treatment bone marrow aspirate revealed low percent residual blasts (3% blasts by flow) with hypocellular BM (5-10% cellularity) and ANC 0.3, platelets 23K
  • Venetoclax was interrupted at this time. Labs checked 2-3 times per week outpatient. Within 12 days after venetoclax interruption ANC>0.5 and platelets>50K.
  • Cycle 2 started outpatient with standard dose azacitidine and venetoclax reduced to 14-21 days

Follow-up

  • Patient subsequently developed pneumonia, treated with oral antibiotics
  • Patient will continue routine bone marrow biopsies after cycle 4, and every 6 months thereafter or if disease progression is suspected