As we near the end of 2023, I think everyone is ready for a break from an exhausting year. 

We came through the COVID pandemic and still remain on alert for what the future may bring. We celebrated the FDA approval of exciting new immune therapies while grappling on how to best use them within a whole complex myeloma treatment landscape. 

Reconnecting in-person has been great, but it will take time to adjust to a new balance of Zoom calls and daily work and travel to visit friends and family. Nothing is quite the same and the chaos and strife in the world around us is hard to bear.

Moving on from the pandemic 

Fortunately, although new COVID-19 variants continue to emerge, prior vaccination plus the new boosters are definitely protecting us against serious disease. It is important to remember the precautions we have learned over these past three years to avoid unnecessary risks of exposure and to stay as safe as possible. The very good news is that we are no longer faced with life-and-death scenarios as we had in the past, although there will still be periods of being unwell while heading towards recovery.

The new myeloma treatment landscape

The recent 2023 ASH Meeting in San Diego brought the myeloma landscape for 2024 into focus. Currently, there are options for the newly diagnosed that have been proven effective. 

Two new phase 3 trials, the PERSEUS and IsKia trials, affirmed the added benefit of using four-drug combinations vs the standard of care(SoC) three-drug combos of Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (VRd); or potentially, KRd (carfilzomib, lenalidomide, and dexamethasone).

Adding anti-CD38 agents daratumumab or isatuximab confers deep and longer responses with acceptable tolerability. Questions shift to access and reimbursement which, hopefully, can be feasible and achievable.

Encouraging news about MRD testing

A number of ASH presentations (especially by the research teams from Salamanca and Pamplona, Spain) introduced data to support the role of blood testing for reliable and sensitive testing for minimal residual disease (MRD). 

Checking to see of any myeloma is present among 100,000 or a million cells counted (10^-5 and 10^-6 sensitivity) can be performed using a blood sample, when cells are concentrated using an immunomagnetic bead approach. 

This can, in fact, give 10^-7 or 10^-8 sensitivity. Then, combining this blood NGF testing (BloodFlow) with very sensitive mass spectrometry techniques to detect very low levels of myeloma protein in the blood identifies patients likely to have very long remissions linked to very deep responses. 

This ability to monitor excellent deep response more easily is a major win for both patients and investigators.

New immune therapies for 2024 

So much was presented at ASH 2023 about new immune therapies that it was hard to keep up! Results from bispecific (even trispecific) antibodies, CAR T, and other cellular therapies illustrated major evidence of treatment efficacy. 

The major challenge is balancing side effects and toxicities to achieve an effective, patient-friendly treatment schedule. Much work needs to be done to assess best sequencing of agents as well as schedules, dosing, and durations of therapy. 

The good news is the International Myeloma Working Group’s (IMWG) Immune Therapy Registry research project will help guide future decision-making in 2024 and beyond.

Is screening the way of the future? 

Follow-up presentations at ASH 2023 from the IMF-supported iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) Project indicated the potential value of screening for the presence of a monoclonal protein (monoclonal gammopathy of undetermined significance or MGUS) in the general population. 

Data illustrated that after screening, the face of myeloma has changed: myeloma patients present with lesser CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities) criteria or evidence of myeloma symptoms. This is a huge benefit. Outcomes are much improved.  Further follow up is required to assess the overall value of screening, but clearly, results so far are very encouraging.

Optimism for 2024

After a well-deserved period of rest and recovery and readjustment, there is much to be optimistic about for 2024 and beyond. 

The landscape for myeloma patients is changing dramatically for the better. Much longer remissions and survival are possible and are expected for a majority of patients. Even for patients with difficulty treating higher-risk disease, there are more options available.

So, let’s enjoy these holiday times with our family and friends, build up our resilience, and renew our energies to take advantage of all the good and positive things that 2024 can bring.