NCCN guidelines focus on treatment options for patients with multiple myeloma

Abstract

The National Comprehensive Cancer Network (NCCN) recently published significant updates specific to treatment options for patients with newly diagnosed multiple myeloma (MM) who are eligible or ineligible for hematopoietic cell transplantation (HCT), recommendations for maintenance therapy, and treatment options for previously treated MM.¹

Based on the most recent clinical evidence, the recommendations are meant to serve as guidelines, and clinicians are encouraged to use their best judgment when applying the recommendations in the context of individual clinical circumstances.

Ajay K. Nooka, MD, MPH, associate director of clinical research at the Winship Cancer Institute at Emory University in Atlanta, Georgia, points to several new updates for oncologists.

Patients who do not meet the criteria for high risk are considered to be at standard risk.²

New updates for the diagnostic workup of MM include renal biopsy for albuminuria or abnormal renal function and the addition of next-generation sequencing for TP53 mutation assessment. The updates also include a revised recommendation for baseline clonotype identification at diagnosis and for the storage of an aspirate sample for future clonotype identification to enable minimal residual disease testing through next-generation sequencing.

The update added daratumumab as a high-risk treatment option based on evidence from the phase 3 AQUILA trial showing that patients treated with subcutaneous daratumumab had a significantly lower risk of progression to active MM.³

The updated recommendations call for the addition of central nervous system disease management, including multimodality therapy, radiation, intrathecal chemotherapy, and systemic chemotherapy, and novel agents such as chimeric antigen receptor (CAR) T-cell therapy.

For primary therapy in patients who are candidates for HCT, the update recommends the quadruple regimen of isatuximab-irfc, bortezomib, lenalidomide, and dexamethasone (Isa-VRd).

For primary therapy in patients for whom HCT is deferred or who are not candidates for HCT, the update recommends either daratumumab, bortezomib, lenalidomide, and dexamethasone or Isa-VRd for patients who are <80 years old and are not frail. Dr Nooka emphasizes that all the treatment recommendations are based on the strongest (category 1) evidence.

The recommendations provide guidance on the treatment of patients in certain circumstances. Patients can receive more than one B-cell maturation antigen (BCMA)–targeted therapy, although the optimal sequencing of sequential BCMA-targeted therapies is not known. Dr Nooka emphasizes, however, that accumulated data suggest that immediately following with the second BCMA-directed therapy after relapse may be associated with lower response rates.

Other circumstances include the use of belantamab mafodotin-blmf (as available through the expanded-access program) and the use of talquetamab plus teclistamab for patients with MM with extramedullary disease.

To calculate the prognosis of older adults with MM, the update recommends using the Myeloma Frailty Score Calculator developed by the IMWG (http://www.myelomafrailtyscorecalculator.net/).

The update recommends more equitable and inclusive clinical trials that include African American and Black people because of the differences in disease biology and responses to treatment found in this population versus White people. African American and Black people have the highest rate of myeloma and differential biology, with most likely to have chromosome 14 translocations (e.g., t(11:14), t(14:16), and t(14:20)) and most less likely to have high-risk mutations (e.g., del(17p) and gain/amp(1q)) compared to White people. Also, the toxicity of drugs can vary in African American and Black people; this includes the hyperpigmentation of skin with the use of immunomodulatory drugs and a higher risk for cytokine release syndromes during CAR T-cell therapy.