Triplet Therapy: A New Standard for Multiple Myeloma

Conference Correspondent —December 20, 2019

Categories:

Multiple Myeloma

Introduction

While new cancer therapies can improve patient outcomes, shifting standards can also lead to problems for healthcare providers, particularly nurses. Working on the frontline of care, nurses need a strong knowledge base to guide patients through their cancer journey, and during the treatment process, to identify and manage drug-related adverse events.1

For multiple myeloma, triplet therapy is a new standard of care that replaces doublet therapy for most patients.2 While adding a third drug may seem simple enough, practitioners need to be aware of unique benefits and risks.

Doublet versus Triplet Therapy

An example of a doublet therapy regimen is shown in Table 1. This particular regimen involves an immunomodulatory agent and a corticosteroid given in a 28-day cycle.3

Table 1: Example Doublet Therapy

Therapy/Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
IMID
(oral capsule)
             
Steroid
(oral capsule)
                               

Triplet therapy typically involves the addition of a proteasome inhibitor.2 An example treatment regimen, with a 21-day cycle, is shown in Table 2.4

Table 2: Example Triplet Therapy

Therapy/Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Proteasome inhibitor
(subcutaneous injection)
                                 
IMID
(oral capsule)
             
Steroid
(oral capsule)
                                   

Efficacy

Compared with doublet therapy, triplet therapy is more likely to generate a response, slow disease progression, and extend survival, as demonstrated by the findings in Table 3.5

Table 3: Outcome Measure/Therapy

Outcome Measure/Therapy Doublet Triplet
Response rate 66.8% 72.7%
Progression-free survival 30 months 43 months
Overall survival 64 months 75 months

Safety

Triplet therapy is more intensive than doublet therapy, which can increase the risk of adverse events.2 Because of this, elderly patients or those with comorbidities may be better suited to doublet therapy.

Beyond the usual side effects seen with steroids, the most common adverse events encountered with triplet therapy are peripheral neuropathy and diarrhea, usually attributed to proteasome inhibitors and immunomodulatory drugs.6,7 For reference, common side effects for these two drug classes are shown in Table 4 below.

Table 4: Drug Classes & Common Side Efects

Drug Class Common Side Effects
Proteasome Inhibitors6
  • Peripheral neuropathy
  • Diarrhea, nausea, constipation, vomiting, reduced appetite
  • Pyrexia
  • Cytopenia
  • Psychiatric disorders
Immunomodulatory Drugs7
  • Diarrhea, constipation, nausea, reduced appetite
  • Cytopenia
  • Insomnia
  • Lethargy
  • Fluid retention
  • Muscle cramp/spasms
  • Abdominal pain
  • Back pain
  • Weakness
  • Pyrexia
  • Infection
  • Cough
  • Rash
  • Dyspnea
  • Dizziness

Managing Diarrhea and Peripheral Neuropathy

Diarrhea

Most cases of triplet therapy–induced diarrhea tend to be mild or moderate, typically occurring within 24 to 48 hours of drug administration and subsiding before the next dose.8 Experts recommend treating diarrhea with dietary fat restriction, antimotility agents, and in some cases, bile acid sequestrants.

Peripheral Neuropathy

Triplet therapy–induced peripheral neuropathy can be serious, potentially leaving patients with irreversible pain and disability.8 No available treatments can resolve peripheral neuropathy, so early intervention is essential, either with reduced drug doses or agent substitutions. For symptom management, gabapentin and pregabalin are typically recommended as first-line options.

Be Specific

With appropriate patient selection and close monitoring, patients with multiple myeloma can benefit greatly from triplet therapy. While the above review provides a cursory look at this treatment space, be sure to review specific drugs used in triplet regimens to ensure optimal patient discussions and management strategies.


References

  1. Faiman B, Kurtin S, Timko J, Gracie-King L. Multiple Myeloma Mentorship: Bridging Communication and Educational Gaps. Clin J Oncol Nurs. 2017;21(1):99-103. doi:10.1188/17.CJON.99-103
  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Multiple Myeloma. Version 3.2019. nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Published June 19, 2019. Accessed July 22, 2019.
  3. Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005;106(13):4050-4053.
  4. Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119(19):4375-4382.
  5. Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527.
  6. Velcade [package insert]. Cambridge, MA: Millennium Pharmaceuticals Inc; 2008.
  7. Revlimid [package insert]. Summit, NJ: Celgene Corporation; 2017.
  8. Paner A, Okwuosa TM, Richardson KJ, Libby EN. Triplet therapies–the new standard of care for multiple myeloma: how to manage common toxicities. Expert Rev Hematol. 2018;11(12):957-973.
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Last modified: November 5, 2020

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