Episode Summary: The Fellow on Call, Episode 143

Podcast: The Fellow on Call: The Heme/Onc Podcast
Episode Title: Myeloma Series, Pt. 4 – Myeloma Pharmacology (2025)
Hosts: Ronuk, Vivek, Dan
Guest: Dr. Catherine Maples, Clinical Pharmacy Specialist, Winship Cancer Institute at Emory Healthcare
Release Date: December 30, 2025

Episode Overview

This episode dives into the nuts and bolts of multiple myeloma pharmacology. The hosts, joined by Dr. Catherine Maples, tackle the key drug classes, regimens, mechanisms of action, toxicities, patient education pearls, and practical management strategies for multiple myeloma therapies. The discussion is aimed at learners and practitioners at all levels, providing high-yield, evidence-based, and patient-centered insights, punctuated with memorable explanations and real-world tips.

Key Discussion Points & Insights

1. Foundations of Multiple Myeloma Regimens (02:17)

• Triplet Regimens:
  Standard initial therapy involves three drugs:

  • Immunomodulatory drug (IMiD): e.g., lenalidomide, pomalidomide (end with "-omide")
  • Proteasome Inhibitor: e.g., bortezomib, carfilzomib, ixazomib (end with "-zomib")
  • Steroid: usually dexamethasone

• Mnemonic: VRD = Velcade (bortezomib), Revlimid (lenalidomide), Dexamethasone

“Know this, Anything that has an omide – lenalidomide, pomalidomide – that is the immunomodulatory drug, also known as an imid … For the proteasome inhibitors, those end in zomib.”
— Vivek (01:22)

2. Bortezomib (Velcade): Neuropathy, Dosing, and Patient Counseling

Mechanisms, Side Effects, Practicalities (06:28)

• Neuropathy:
  • Most frequent within the first five cycles (06:28)
  • Can be cumulative, but rarely appears later if not noticed early
  • Graded (CTCAE): interventions depend on severity and whether there is pain
  • Management: dose reduce or hold (esp. grade 2 with pain), and treat symptoms (gabapentin, pregabalin, duloxetine)

“We can’t prevent it … We really rely on the patient letting us know when they are experiencing it so we can make interventions.”
— Dr. Catherine Maples (06:28)

• Patient Education:

  • Encourage non-suffering in silence; specific questions about daily tasks
  • Standard neuropathy meds used; vitamin B and supplements lack strong evidence

• Other Key Side Effects:

  • Herpes zoster reactivation (antiviral prophylaxis mandatory)
  • Diarrhea or constipation (often more diarrhea with IMiDs)
  • Unique: styes (treated with doxycycline)

• Relevant Drug Interactions:

  • Vitamin C (>500mg) and green tea can antagonize efficacy (11:00)
  • Ask about over-the-counter supplements not listed on med lists

“The data shows that anything over 500mg of vitamin C can cause the inhibition. So I ask [patients] to look at their multivitamin.”
— Dr. Catherine Maples (10:01)

• Dosing:
  • Twice weekly vs. once weekly: similar overall dose intensity; twice weekly may be favored for induction in younger, fitter patients to achieve deeper responses (12:30)

3. Lenalidomide (Revlimid): Mechanism & Side Effects

From Immunomodulation to Real-World Dosing (15:59)

• Mechanism of Action:
  • Multifactorial: Direct cytotoxicity (via cereblon), anti-angiogenesis, immune modulation (NK and T cell activity) (15:59)

“It does directly kill the myeloma cells, it helps your immune system kill the myeloma cells, and then it also shrinks those blood vessels just to prevent growth.”
— Dr. Catherine Maples (16:44)

• Key Toxicities:

  • Rash: immune, often appears during maintenance, may require topical steroids or Medrol dose pack but rarely discontinuation
  • Diarrhea: due to bile acid malabsorption, better managed with bile acid sequestrants than with loperamide (18:43)
  • Cytopenias/fatigue: main reason to dose reduce, esp. in maintenance rather than induction (growth factors can be used)

• Dosing Philosophy:

  • In younger, fit, transplant-eligible patients, try to start at 25mg unless significant renal dysfunction
  • For frailer or older patients, consider starting lower (10–15mg), guided by “gut feeling” (20:56)

4. IMiD REMS Program & Dispensation Logistics (22:50)

• REMS Overview:

  • Risk Evaluation and Mitigation Strategy mandated due to thalidomide’s teratogenicity legacy
  • Requirements:
    • Females of child-bearing age: negative pregnancy test before every refill; log into portal for authorization code
    • All patients: must use two forms of contraception (one barrier)
    • Online survey prior to each dispensation; must be passed for pharmacy to release drug

• Insurance & Access:

  • Prior authorizations, financial copay assistance adds to complexity

“All the patients, men and women, have to complete a survey before the pharmacy can dispense the drug to them.”
— Dr. Catherine Maples (25:28)

5. IMiDs and Clot Risk: DVT Prophylaxis (26:43)

• Who’s High Risk?
  • Prior history of thrombosis is a key factor
  • Use scoring systems (IMPEDE, SAVED) to stratify risk (26:43)
  • Low-risk: baby aspirin may suffice
  • Higher risk: low-dose DOAC (half-dose apixaban/rivaroxaban)

6. Dexamethasone Schedules & Counseling (28:49)

• Simplifying Regimens:
  Modern schedules strive for simplicity: e.g., consolidate doses to infusion days vs. older scattered schedules

• Counseling Pearls:

  • Try to give dex at infusion center; split doses if “dex crash” next day is problematic

“If we can try to make the dex easier for them and just give it to them when they're already here for their Velcade or their Dara, that tends to be more successful.”
— Dr. Catherine Maples (29:38)

7. Daratumumab (Dara): Mechanism & Administration (31:43)

• Mechanism of Action:

  • Targets CD38 on myeloma and other cells
  • Triggers cell death via immune-mediated mechanisms (ADCC, CDC, etc.)

• Practicalities:

  • Pre-treatment type & screen is essential (impacts Coombs test)
  • Subcutaneous formulation is now preferred:
    • No test dose required
    • Far fewer infusion reactions vs. IV
    • Five-minute injection (larger volume than standard SC, but quick) (33:42)

• Infection Risk & Vaccination:

  • Increased risk for URIs and other infections; ensure flu, COVID, pneumonia vaccines are up to date
  • IVIG for recurrent infections or low IgG (<400) considered (34:04)

8. Management in Renal Dysfunction: CyBorD, IMiDs, and Alkylators (35:10)

• Acute Renal Dysfunction:

  • Aim: rapid myeloma control to rescue renal function
  • CyBorD (cyclophosphamide, bortezomib, dexamethasone) typically used; twice-weekly bortezomib preferred unless patient is frail

• Cyclophosphamide:

  • Oral vs. IV: Oral often favored for speed, but may require swallowing many pills (38:05)

• Switching to Lenalidomide:

  • Not nephrotoxic, just renally cleared; monitor for cytopenias
  • Dosing is conservative per PI, but some evidence for higher doses is referenced
  • Consider switching to lenalidomide when GFR >30–40 (38:21)
  • Thalidomide can be used in dialysis/poor renal function – doesn’t require adjustment

9. Carfilzomib (Kyprolis): Cardiotoxicity–But Little Neuropathy (41:36, 43:59)

• Main Concern:

  • Hypertension, potential for heart failure/TMA, headaches on infusion days, thrombocytopenia (41:36)
  • Usually premedicate with low-dose steroids to prevent reactions
  • Neuropathy is rare (43:59)

• Dosing:

  • Once-weekly regimens are now supported by data (ARROW study); no increased cardiotoxicity, may be more tolerable (43:15)

10. Pomalidomide and Other Second-Line Agents (44:49, 45:18)

• Pomalidomide (Pomalyst):
  • Greater myelosuppression than lenalidomide
  • Less diarrhea and rash
  • Can be used with dose adjustments in renal failure (45:31)

11. Supportive Care: HSV and PJP Prophylaxis (45:52)

• Who Needs HSV Prophylaxis?

  • Anyone on a proteasome inhibitor or monoclonal antibody regimen
  • Velcade, carfilzomib, daratumumab, isatuximab, elotuzumab

• PJP Prophylaxis:

  • Based on steroid dose: recommended if receiving dex ≥20mg/week
  • Also for stem cell transplant, bispecifics, and CAR-T patients due to higher risk of opportunistic infections

“It’s not just their myeloma therapy, but HSV prophylaxis is recommended for anybody on a proteasome inhibitor– or monoclonal antibody–based regimen.”
— Dr. Catherine Maples (46:15)

Notable Quotes & Memorable Moments

• On Bortezomib Neuropathy:

  “I need them to not suffer in silence, but let us know … so that we can properly grade the peripheral neuropathy and make dose holds or dose reductions appropriately.”
  — Dr. Catherine Maples (06:39)

• On Patient Questions:

  “Can you button your shirt, can you open a water bottle? Trying to get a feel for how it’s impacting their daily is key…”
  — Dr. Catherine Maples (08:08)

• On Dosing Philosophy:

  “I think it’s definitely an eyeball and gut feeling as well.”
  — Dr. Catherine Maples (21:28)

• On Logistics:

  “It is a lot of steps to make sure that the pregnancy test is done, the survey is done, and the prescriptions are filled in a timely manner.”
  — Dr. Catherine Maples (25:28)

• On Daratumumab SubQ:

  “SubQ DERA does not require a test dose. … It's a five-minute push, which … is a bit unique to a SubQ drug. … There are significantly less infusion related reactions.”
  — Dr. Catherine Maples (33:42)

• Hosts Recap:

  “For her, it’s probably very simple, but for us … it’s so, so helpful.”
  — Vivek (48:11)

Important Timestamps

• Triplet regimen/abbreviation breakdown: 02:17
• Bortezomib neuropathy explanation: 06:28
• Vitamin C/green tea drug interaction: 11:00
• Weekly vs. biweekly bortezomib: 12:30
• Lenalidomide mechanism: 15:59
• Rash & diarrhea with lenalidomide: 17:43
• IMiD REMS logistics: 22:50
• Clot risk and DVT prophylaxis: 26:43
• Dexamethasone schedules: 28:49
• Daratumumab SC vs. IV, mechanism: 31:43
• Infection risks & vaccines with Dara: 34:04
• CyBorD in renal failure: 35:10
• Cyclophosphamide oral vs. IV: 37:14
• Criteria for switching to lenalidomide: 38:21
• Carfilzomib side effects: 41:36
• Neuropathy with carfilzomib: 43:59
• Pomalidomide profile: 44:49
• Supportive care (HSV, PJP): 45:52

Closing Thoughts

This episode is a comprehensive, clinic-friendly, and learner-focused roadmap through the pharmacology of myeloma therapy. Listeners gain not only a solid grasp of the mechanisms and toxicities but also invaluable tips for effective patient counseling, risk mitigation, and logistical challenges in real-world practice.