The Fellow on Call: The Heme/Onc Podcast

Episode 143: Myeloma Series, Pt. 4 – Myeloma Pharmacology (2025)

Release Date: December 24, 2025
Hosts: Ronuk (A), Vivek (B), Dan (C)
Guest Expert: Dr. Catherine Maples, PharmD (D), Clinical Pharmacy Specialist, Winship Cancer Institute at Emory Healthcare

Episode Overview

In this in-depth episode of The Fellow on Call, the hosts are joined by Dr. Catherine Maples, a myeloma-focused clinical pharmacist, to break down the pharmacology of multiple myeloma treatments. The discussion centers on understanding drug classes, mechanisms, side effects, patient counseling, and special considerations in both standard and complex clinical scenarios—offering practical pearls for trainees and practicing providers alike.

Key Discussion Points and Insights

1. Common Drug Classes and Regimens Used in Myeloma

• Triplet therapy is standard, usually comprising:
  • Immunomodulatory drugs (IMIDs): lenalidomide, pomalidomide (suffix "-omide")
  • Proteasome inhibitors: bortezomib, carfilzomib, ixazomib (suffix "-zomib")
  • Steroids: typically dexamethasone
• Brand/generic names: Bortezomib = Velcade (hence, VRD regimen is Velcade, Revlimid, Dexamethasone).

“In myeloma, the standard is triplet regimens. … Anything that has an omide, lenalidomide, pomalidomide, that is the immunomodulatory drug, also known as an imid."
—Vivek (B), [01:22]

2. Detailed Drug Profiles and Practical Tips

A. Bortezomib (Velcade): Neuropathy and Patient Counseling

• Main side effect: peripheral neuropathy—cannot be prevented, so close patient reporting is vital.
• Timing:
  • Neuropathy most often occurs within the first 5 cycles. If absent after 5 cycles, risk diminishes, though can rarely occur later.
  • Management: Hold or reduce dose if grade 2 neuropathy with pain. Start with gabapentin, escalate to pregabalin or add duloxetine as needed.
• Other key counseling points:
  • Herpes zoster/HSV reactivation risk—antiviral prophylaxis is a must.
  • Drug interactions with vitamin C (>500mg) and green tea can interfere with the drug.
  • GI issues can be constipation or diarrhea.
  • Unique side effect: styes (treated with doxycycline).
• Subcutaneous (SubQ) dosing reduces neuropathy compared to IV but still must be administered at a chemo center.

"We can't prevent it... So we really rely on the patient letting us know when they are experiencing it so that we can make interventions." —Dr. Maples (D), [06:28]
"Anything over 500 milligrams of vitamin C can cause the inhibition. So I ask them to look at their multivitamin..." —Dr. Maples (D), [11:00]

B. Lenalidomide (Revlimid): Mechanism, Side Effects, and REMS

• Mechanism: Multifactorial; direct tumor cytotoxicity, immunomodulation via T/NK cells, anti-angiogenesis. Newer agents target cereblon.
• Side effects:
  • Rash (immune based, can occur after steroids stopped; treat with topical steroids or Medrol dose pack).
  • Diarrhea (due to bile acid malabsorption; treat with cholestyramine/"bile acid sequestrant" over Imodium).
  • Myelosuppression (cytopenias)—manage with growth factors during induction if necessary, or dose reduce in maintenance.
  • Fatigue.
  • Dose reduction based on toxicity and patient frailty.
• REMS Program: Strict risk mitigation due to teratogenicity.
  • Requirements: negative pregnancy test before every fill, two forms of birth control (one barrier), patient surveys before dispensing.

"For a long time no one had any idea [how it works]…it does directly kill the myeloma cells, helps your immune system kill the myeloma cells and then also shrinks blood vessels..." —Dr. Maples (D), [15:59]
"REMS stands for Risk Evaluation and Mitigation Strategy...based off of the safety of the drug." —Dr. Maples (D), [22:50]

C. Dexamethasone: Dosing Simplification

• Schedules have improved and become less complex; aim to administer in-center and reduce take-home dosing.
• Side effects and patient “crash” can occur; doses can be split between infusion center and home.

"If we can try to make the dex easier for them and just give it to them when they're already here...that tends to be more successful." —Dr. Maples (D), [28:49]

D. Daratumumab (Dara): Mechanism, Administration, and Infections

• Mechanism: Depletes CD38-positive plasma cells, has multiple immune-mediated actions.
• Infusion reactions: SubQ dosing is preferred—lower rate of reactions, quick 5-min injection (no test dose required, unlike rituximab; but higher volume than typical SubQ drugs).
• Precautions: Causes pan-agglutination/interferes with blood typing (indirect Coombs).
• Vaccination: Ensure influenza, COVID, and pneumonia vaccines are updated. Consider IVIG if hypogammaglobulinemia or recurrent infections.

"Sub Q Daratumumab definitely has changed the game...it's a five-minute push...and there are significantly less infusion related reactions." —Dr. Maples (D), [31:43]
"Making sure patients are up to date on their vaccines, the flu vaccine, Covid and then pneumonia..." —Dr. Maples (D), [34:04]

E. Alkylators & Alternative Regimens for Renal Dysfunction

• CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone) is used for patients with renal insufficiency, as lenalidomide is renally cleared.
• Cyclophosphamide: Oral and IV options—oral often preferred for shorter infusion, but large capsule burden.
• Thalidomide: Useful in severe renal impairment as it does not require renal adjustment and is still used in select regimens (esp. in European practice or for patients on dialysis).

"Lenalidomide is not nephrotoxic. It's just cleared renally...if a patient has impaired renal function, you're going to get a buildup of the drug and higher toxicities." —Dr. Maples (D), [38:21]

F. Carfilzomib (Kyprolis): Toxicities and Dosing

• Main concern: Cardiotoxicity (HTN, heart failure), possible TMA.
• Dosing: Once-weekly dosing (per A.R.R.O.W trial) is favored—no increase in cardiovascular events, more convenient.
• Rare neuropathy: Unlike bortezomib, carfilzomib has minimal neurotoxicity.

"We can see a variety of different cardiotoxicity with carfilizomib ranging from hypertension all the way to heart failure." —Dr. Maples (D), [41:36]
"We use a lot more once weekly dosing regimens in the relapse setting for patients...and that can help with some of those day to day side effects..." —Dr. Maples (D), [43:59]

G. Pomalidomide (Pomalyst):

• Compared to lenalidomide, pomalidomide causes more myelosuppression but less diarrhea or rash.
• Adjustments needed in renal impairment; can be considered even in patients on dialysis.

"We do see much more neutropenia and thrombocytopenia compared to revlimid...the fatigue and the myelosuppression I think are much more potent with pom." —Dr. Maples (D), [44:49]

3. Supportive Care and Prophylaxis

A. Antiviral Prophylaxis

• HSV/VZV prophylaxis (e.g., acyclovir, valacyclovir) is mandatory with:
  • Proteasome inhibitors (bortezomib, carfilzomib)
  • Monoclonal antibodies (daratumumab, isatuximab, elotuzumab)

B. Thromboembolism Prophylaxis

• IMIDs increase risk of DVT/PE.
• Use validated risk scores (IMPEDE, SAVED) and clinical judgement.
  • Low risk: ASA 81 mg vs. high risk: low-dose apixaban or rivaroxaban.

"One of the biggest risk factors for a clot on an IMID is having any prior history of a clot...most of the time we do half-dose apixaban or rivaroxaban." —Dr. Maples (D), [26:43]

C. PJP Prophylaxis

• For patients on steroids equivalent to ≥20 mg prednisone daily for ≥30 days (e.g., dex 20 mg weekly).
• Also post-autologous stem cell transplant or for those receiving CAR-T/bispecifics.

"If they're on a regimen of dex 20 milligrams weekly or higher, then I would recommend PJP prophylaxis." —Dr. Maples (D), [46:17]

Notable Quotes & Memorable Moments

• "Don't suffer in silence. Let us know and inform us when you start to feel these sensations so that we can properly grade the peripheral neuropathy and make dose holds or dose reductions appropriately."
  —Dr. Maples (D), [06:28]

• “It's not like on their last day of revlimid they can stop practicing [contraception]. Four weeks later would be the cutoff for that.”
  —Dr. Maples (D), [25:05]

• “The paradigm really is just let's blast this disease out of water, see if we can't get some kidney function back.”
  —Dan (C), [38:06]

• “There are so many ways to treat multiple myeloma, so many different trials, there's so many ways to slice and dice this. But it's really good to know, to hear to how people practice differently.”
  —Vivek (B), [40:32]

Important Segment Timestamps

• [02:44] — Introductions and case setup
• [06:28] — Peripheral neuropathy counseling for bortezomib
• [11:00] — Unique drug interactions: Vitamin C and Velcade
• [15:59] — IMID mechanism of action explained
• [17:43] — Lenalidomide side effects and dose reduction strategies
• [22:50] — The REMS program for IMIDs
• [26:43] — DVT risk with IMIDs and prophylaxis
• [28:49] — Dexamethasone scheduling and patient guidance
• [31:43] — Daratumumab: subcutaneous administration, mechanisms, and reactions
• [38:21] — Myeloma therapy adjustments for renal dysfunction
• [41:36] — Carfilzomib: Cardiovascular risks and monitoring
• [44:49] — Pomalidomide vs. lenalidomide toxicity
• [46:17] — Antiviral and PJP prophylaxis in myeloma

Summary Tone

The conversation is collegial and educational, blending practical pearls from Dr. Maples' pharmacy expertise with the hosts’ clinical questions and curiosities. The episode makes complex pharmacology approachable for learners at any stage while emphasizing patient-centered care and multidisciplinary collaboration.

Listen to this episode if:

• You want a clear, practical walk-through of frontline and supportive myeloma drugs, their side effects, and real-world management.
• You need insights on how pharmacists collaborate in the care team.
• You’re a trainee seeking “the why” behind pharmacology choices or curious about evolving standards in myeloma therapy.