The Differential: A CNS relapse of AML, the benefit of ivosidenib in mIDH1 AML, and more

Director of the Leukemia Program at Cleveland Clinic and Vice Chair for Clinical Research at the Taussig Cancer Institute.

Welcome to The Differential! I'm excited to be the new editor of this high-quality newsletter that brings you the top stories in hematology/oncology every two weeks, curated by physicians for physicians. The Differential is designed to be quick (skim it in just a few minutes) and thorough (all the information you need is in this email). In this issue, find a new, targeted approach to treating older adults with acute myeloid leukemia and an IDH1 mutation that avoids traditional chemotherapy altogether.

- Mikkael Sekeres

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1. In patients with newly diagnosed mIDH1 AML (median age, 76 years), ivosidenib monotherapy achieved median overall survival of 12.6 months.  Read the study

2. The benefit of gemtuzumab ozogamicin in non-CBF AML patients with favorable or intermediate ELN 2017 risk is restricted to those with signaling mutations.  Read the study

3. A loss-of-function polymorphism in IL6R reduces risk of JAK2V617F mutation and myeloproliferative neoplasm, supporting inflammation as an independent risk factor for JAK2V617F mutation and myeloproliferative neoplasm. Read the study

4. The American Society of Clinical Oncology (ASCO) announced its support for drug repository programs, to help reduce the nearly $3 billion that is lost annually to cancer drug waste, with the condition that they will be for oral medications maintained within a closed system. Read the article

5. What to do when your grant is rejected. Read the article

CLINICAL DIGEST: In Case You Missed It

This 26-year-old was diagnosed with AML three years ago

He initially presented with leukocytosis and fevers, the karyotype was der(1;7)(q10;p10), and next-generation sequencing showed mutation in KRAS codon 12. He was treated with conventional induction chemotherapy with daunorubicin 90 mg/m2/d x 3 and cytarabine 100 mg/m2/d x 7, and achieved remission. He then underwent transplant.

A year ago, he developed headaches, fatigue, and nausea. His blood counts were normal. On exam there was no evidence of leukemia cutis or focal neurological deficits. Marrow biopsy was normal with full donor chimerism. CSF showed an increased WBC count with 77% blasts that are positive for CD45(dim), CD13, CD15 and CD56(dim), and very dim for CD117. He was treated with intrathecal chemotherapy serially until clearance for CNS relapse, followed by donor lymphocyte infusion. Recurrence of CNS symptoms and abnormal cytology led to treatment with high-dose cytarabine, then radiation, and then high-dose methotrexate, then nivolumab on a clinical trial. He now presents with another CNS recurrence.

What would you do next?

Quiz: What lab finding is most likely?

A 14-year-old boy is brought to the pediatrician by his mother over concerns of difficulty walking and worsening clumsiness. He reports a gradual loss of night vision, and a long history of chronic diarrhea which is pale and foul-smelling. Examination reveals an ataxic gait, and loss of deep tendon reflexes. Bilateral retinitis pigmentosa is noted on fundoscopy and a peripheral blood smear reveals the findings seen here.

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