72-Year-Old Man with Heavily Pretreated RRMM

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EP: 1.72-Year-Old Man with Heavily Pretreated RRMM

EP: 2.Treatment Options for Heavily Pretreated RRMM

EP: 3.The DREAMM-2 Trial in RRMM

EP: 4.Role of Belantamab Mafodotin In the Treatment of Heavily Pretreated RRMM

EP: 5.Current Status and Future Directions in RRMM

Sagar Lonial, MD, FACP: Let’s start off with a case of heavily pretreated relapsed/refractory myeloma. A 72-year-old man [received an initial diagnosis of] myeloma about 4.5 years ago and returned for routine follow-up. His treatment history included initially being treated with bortezomib, lenalidomide, and dexamethasone [VRd] for about 12 months, followed by lenalidomide maintenance daily. He achieved stable disease that lasted for approximately 36 months. After progression, he was subsequently rechallenged with VRd and achieved stable disease again, [which lasted] about 20 months. He was then switched to carfilzomib with pomalidomide and dexamethasone [KPd] and achieved a partial response that lasted approximately 15 months. Then he was switched to daratumumab, bortezomib, and dexamethasone [DVd]. His follow-up at 12 months showed an M protein increase of approximately 0.5 g/dL, but he continued to do well. However, 3 months after that visit, he came back to the clinic complaining of increased muscle weakness, fatigue, and bone pain. His physical exam showed new bone tenderness on his ribs, as well as bruising and mild bleeding of his gums. His clinical work-up at that time showed a hemoglobin of 8.8, calcium of 10.2, and LDH of 160; [his] creatinine was 2.1, albumin was 3.0, β-2 microglobulin was 4.9, and the M protein was now 4.2 g/dL with λ free light chains of about 4.1 mg/kg. Hepatitis B was negative. Skeletal survey and MRI demonstrated stable lytic lesions in the left hip, pelvis, and L2, as well as new lytic lesions on ribs 4 and 10 on the left side. Bone marrow showed about 70% plasma cells with IgG [immunoglobulin G] κ restricted, and FISH [fluorescence in situ hybridization] analyses demonstrated 6/14 translocation, which was present at diagnosis but now demonstrated the presence of 17p deletion. Diagnosis at this time was R-ISS [Revised

Multiple Myeloma International Staging System] stage 2. He had an ECOG performance status of 1. Initiation of treatment with belantamab mafodotin was started based on this history and the need for initial therapy.

[A case such as this] is not uncommon in routine clinical practice. Despite the fact that we have improved the overall survival median for most patients to greater than 10 years, patients who are not potentially eligible or offered high-dose therapy and transplant often have a shorter initial duration of response and often have a shorter overall survival. The fact that this patient has been exposed to all approved classes of drugs and has developed what we call triple-class refractory myeloma is an unfortunate scenario that’s occurring with increasing frequency. What we know from retrospective data analyses is that patients with triple-class refractory myeloma have a median overall survival of less than 1 year and have a median progression-free survival with their next line of treatment in the absence of new drugs of less than 3 months; that includes recycling combinations of cytotoxic agents or recycling of old agents in the past.

One of the main challenges that remains when we see these kinds of patients relates to the fact that their performance status may be limited; their counts may be low as a consequence of progression of disease, as well as multiple rounds of therapy, so they have less bone marrow reserve. These factors together cultivate the idea that although we like to achieve complete remissions or MRD [minimal residual disease] negativity in many of our patients, in patients such as this, achieving stable disease or better with a treatment that is well tolerated can often be a big win and represents a major step forward. The goals of treatment and challenges of patients in this situation are different, and they need to be handled differently. Even if they weren’t frail at the [time they received the] initial diagnosis, they often fall into a frail patient category by the time they’ve reached 4 prior lines of therapy and are triple-class refractory.

Transcript edited for clarity.

A 72-Year-Old Man with Heavily Pretreated, R/R Multiple Myeloma

Initial Presentation

• A 72-year-old man diagnosed with multiple myeloma 4.5 years ago returns for routine follow up
• Treatment history:
  • Initially treated with VRd for 12 months, followed by lenalidomide maintenance 15 mg daily; stable disease lasting 36 months
  • Rechallenged with VRd, stable disease lasting 20 months
  • Subsequently switched to KPd, achieved a partial response lasting 15 months
  • Started DVd; follow up at 12 months showed M protein increase by 0.5 g/dl; patient continues to feel well 
• Currently, 3 months after his last visit, he returns to the clinic complaining of increased muscle weakness, fatigue and bone pain
• PE: new bony tenderness appreciated on ribs, bruising, mild bleeding of the gums

Clinical Workup

• Labs: Hb 8.8 g/dL, calcium 10.2 mg/dL, LDH 160 U/L, creatinine 2.1 mg/dL, albumin 3.0 g/dL, b2 microgloblulin 4.9 mcg/mL, serum M-protein 4.2 g/dL, lambda free light chains 4.1 mg/dL
• HBV negative
• Skeletal survey and MRI revealed stable lytic bone lesions in the left hip, pelvis and L2 vertebrae and new lytic lesions on the ribs 4 and 10 on the left side
• Bone marrow shows 70% plasma cells IgG k
• FISH: t(6;14) (p21;q32) at diagnosis; new del(17p)
• Diagnosis: R-ISS stage II MM
• ECOG 1

Treatment

• Initiated treatment with belantamab mafodotin