Selective Immunomodulating Microtubule Binding Agents (SIMBA): A Novel Approach To Chemotherapy-Induced Neutropenia - Episode 3

CIN Severity and Management

Implications of severity and sequelae of chemotherapy-induced neutropenia for disease management.

Joyce O’Shaughnessy, MD: [What’s serious] with the consequences of chemotherapy-induced neutropenia and how it’s graded? What’s your [feeling about] that, Andy?

Andrew D. Seidman, MD: It’s depth and duration. We certainly have data that grade 4 neutropenia of any duration are more likely to result in the event of febrile neutropenia than grade 3. An ANC [absolute neutrophil count] of less than 500 per mm3. Then the time under a specific threshold, whether it’s 1000 or 500 per mm3. Certainly 7 days of neutropenia is a long time to be neutropenic and increases the risk of infection. On top of that, I’d also say agents that we know affect GI [gastrointestinal] mucosal integrity, which also creates a portal of entry for bacteria. That combination is particularly worrisome.

Joyce O’Shaughnessy, MD: Grade 3 is an absolute neutrophil count under 1000 per mm3,and grade 4 is under 500 per mm3. Classically that’s been such an important end point in the trials of the percentage of patients with grade 4, and this is severe neutropenia. But 1 that’s so clinically relevant is this idea of severe neutropenia, which is when the absolute neutrophil count under 100 per mm3. Wow, that’s a dreaded deal. As we know, those tend to develop very rapidly. That’s when the neutrophil count is dropping like a rocket. In my experience, that’s frightening. It oftentimes results in mucositis, GI toxicity, and diarrhea, which is a very serious issue. The problem, as we pointed out, is we have uncertainty. We have uncertainty about who’s going to do what until you get in there. But that as an end point is very clinically meaningful.

Andrew D. Seidman, MD: Patients who are referred feel malaise but have been taking their temperatures at home; they don’t have a fever. They show up in your emergency department or your urgent care center with extreme neutropenia—an ANC [absolute neutrophil count] of 0.1, for example. Even in the absence of a fever, when those patients don’t look well, they get admitted to the hospital for good reasons.

Joyce O’Shaughnessy, MD: We all know that. We all know we don’t check it to prevent prophylactically in patients. We usually wait until we get a phone call in the curative setting.

Transcript edited for clarity.