Relapse Management

What does myeloma relapse mean?

Biochemical relapse—identified by a 25% rise and absolute increase of ≥ 5 g/L in serum M-protein—typically precedes physical symptoms by 3 to 9 months, offering a crucial window to adjust therapy before permanent organ damage occurs.

What should I discuss when relapse is suspected?

• (1) Biochemical Relapse vs. Clinical Relapse (When to start treatment): A relapse can happen in two ways. A "biochemical" (or serological) relapse means your doctors have noticed a rising M-protein level in your blood or urine, but you feel completely fine. A "clinical" relapse means the disease is causing new physical symptoms or organ damage, such as new bone lesions, anemia, or kidney dysfunction. You do not have to wait until you feel sick to start treatment; guidelines strongly recommend starting therapy during a rapid biochemical relapse to stop the myeloma before it can cause new organ damage.
• (2) The Concept of "Class Switching": Myeloma cells are smart and can become "refractory," meaning they learn how to resist the drugs you are currently taking. To outsmart the cancer, doctors use "class switching." For example, if your myeloma progressed while taking lenalidomide (an immunomodulator), your doctor will switch you to a completely different class of drug (like a monoclonal antibody or a proteasome inhibitor) or use a next-generation drug in the same family (like pomalidomide). As a general rule, to get the best results, doctors will try to use medications you have never had before, or at least ones you have been off of for more than 6 months.
• (3) The Role of Triplet or Quadruplet Regimens at First Relapse: When you experience your first relapse, the goal is to hit the disease hard to achieve the deepest possible remission. Clinical trials have consistently proven that using a "triplet" (3-drug) combination significantly improves how long the disease stays controlled compared to using just two drugs. Depending on what you had previously, your doctor will likely recommend a powerful triplet, such as Daratumumab or Isatuximab combined with Carfilzomib and Dexamethasone.
• (4) The Integration of Advanced Therapies for Later Relapses: If your myeloma returns multiple times, there is still great hope. For patients who have had at least 3 or 4 prior therapies (typically including a proteasome inhibitor, an immunomodulator, and an anti-CD38 antibody), incredible advanced immunotherapies are now available.

  • CAR T-cell Therapy: This involves re-engineering your own immune cells to hunt down myeloma. Therapies like Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have shown massive success. For instance, in heavily pretreated patients, Ide-cel achieved a remarkable 73% overall response rate (with 33% achieving a complete response or better) and a median time to response of just 1 month.
  • Bispecific Antibodies: These are "off-the-shelf" drugs (like teclistamab, elranatamab, and talquetamab) that act like a bridge, grabbing your immune T-cells with one arm and attaching them directly to the myeloma cells with the other arm so your immune system can destroy the cancer.
  • Where these are actually available: Approval does not equal access, and access differs by country. If you are considering treatment in mainland China, which CAR-T products are approved there, which hospitals are licensed to give them, and what they cost is documented separately.
• (5) Importance of Re-evaluating Patient Fitness and Disease Risk: Your myeloma's "personality" can change over time. At every relapse, it is absolutely essential for your team to perform a full reassessment. They will likely order a new bone marrow biopsy with FISH testing to see if the myeloma has acquired any new high-risk genetic mutations (like del(17p) or a 1q gain). Just as importantly, they will re-evaluate you—considering your age, physical frailty, kidney function, any lingering side effects from past treatments, and your personal goals of care. This ensures that your new treatment plan is perfectly tailored to your current life and body.

The above content is sourced from the following references

• Management of relapsed multiple myeloma: A British Society of Haematology and UK Myeloma Society guideline
• EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma
• NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma
• NCCN Guidelines for Patients® Multiple Myeloma
• European Myeloma Network Group Consensus Statement on the use of next-generation sequencing in multiple myeloma