Relapse Management
Navigating the Next Steps
Medical Disclaimer: The following content is compiled based on the latest authoritative guidelines at home and abroad. It is for reference only for patients and their families and cannot replace the professional medical advice of the attending physician. Please be sure to follow the doctor's advice for the treatment plan.
Core Conclusion
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.
Detailed Points
- (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.
- (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
FAQs
- Does a relapse mean treatment has failed?
- No. Myeloma is expected to relapse and remit over time. A relapse means it is time to pivot to a new strategy, and the toolkit of combination therapies and immunotherapies keeps expanding.
- What is the difference between biochemical and clinical relapse?
- A biochemical relapse is a rising M-protein in blood or urine while you still feel well. A clinical relapse means new symptoms or organ damage, such as bone lesions, anemia, or kidney problems. Guidelines recommend starting therapy during a rapid biochemical relapse so the disease does not cause new organ damage.
- What is class switching?
- Myeloma cells can become refractory, meaning they learn to resist the drugs you are taking. Doctors then switch to a different drug class or a next-generation drug in the same family. Results are usually best with medicines you have never had, or at least ones you have been off for more than 6 months.
- Why are three-drug combinations used at first relapse?
- The goal at first relapse is a deep remission. Trials have shown that a three-drug combination keeps the disease controlled longer than two drugs. A common example is daratumumab or isatuximab with carfilzomib and dexamethasone.
- What options exist if myeloma returns several times?
- After at least 3 or 4 prior therapies that typically included a proteasome inhibitor, an immunomodulator, and an anti-CD38 antibody, CAR-T and bispecific antibodies are available. In heavily pretreated patients, ide-cel had a 73% overall response rate, and 33% reached a complete response or better. Bispecifics such as teclistamab, elranatamab, and talquetamab attach T-cells directly to myeloma cells.
- Why do I need another full workup at relapse?
- The myeloma's personality can change. A new marrow biopsy with FISH looks for new high-risk genetics such as del(17p) or a 1q gain. Your team will also reassess your fitness, kidney function, lingering side effects, and personal goals before choosing the next plan.
Related reading
References used for this guide
- 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
Active Clinical Trials for Biochemical and Clinical Relapse
Key multi-center trials available when documented disease progression occurs:
A Randomized, Controlled, Double-Blind, Multicenter Phase III Clinical Trial Evaluating the Efficacy and Safety of SG301 Injection Combined with Pomalidomide and Dexamethasone Versus Placebo Combined with Pomalidomide and Dexamethasone in the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM)
This project is a Phase III clinical trial sponsored by Hangzhou SJ Biosciences Co., Ltd. (Hangzhou Shangjian Biotechnology Co., Ltd.), primarily targeting participants with relapsed/refractory multiple myeloma (RRMM) who have received at least 1 prior line of therapy, have not previously received pomalidomide, and whose prior anti-CD38 antibody therapy was not determined to be refractory/ineffective. The treatment regimen utilizes an anti-CD38 monoclonal antibody (SG301 injection) combined with an immunomodulator (pomalidomide) and a glucocorticoid (dexamethasone), administered in 4-week (28-day) cycles until disease progression or intolerable toxicity. The trial is being conducted across a total of 78 top domestic hospitals in China, including the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences; The First Affiliated Hospital of Soochow University; Beijing Chaoyang Hospital, Capital Medical University; The Second Affiliated Hospital, Zhejiang University School of Medicine; and Sun Yat-sen University Cancer Center, among others.
A Phase III, Randomized Study Comparing JNJ-79635322 and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy (Including an Anti-CD38 Antibody and Lenalidomide)
This study aims to evaluate the efficacy and safety of JNJ-79635322 versus teclistamab in the treatment of multiple myeloma. The trial mainly enrolls adult participants with relapsed or refractory disease who have received 1 to 3 prior lines of anti-myeloma therapy (including an anti-CD38 antibody and lenalidomide). Eligible participants will be randomized to receive subcutaneous injections of JNJ-79635322 or teclistamab. This is an international multicenter study conducted simultaneously in multiple hospitals, including the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences.
A Multicenter, Randomized, Controlled, Open-Label, Phase III Clinical Study of IBI3003 Versus Investigator's Choice of Regimen (DPd or PVd) on the Efficacy and Safety in Participants with Relapsed or Refractory Multiple Myeloma
This study is a multicenter, randomized, controlled, open-label Phase III clinical study in patients with relapsed or refractory multiple myeloma. The study aims to evaluate the efficacy and safety of IBI3003 compared with investigator's choice of regimen (DPd or PVd). The trial is open to participants aged 18 and older who meet the eligibility criteria, and is conducted across multiple hospitals including Zhongshan Hospital, Fudan University.
A Two-Stage, Randomized, Multicenter, Controlled, Open-Label, Phase III Study Comparing Iberdomide Maintenance Therapy with Lenalidomide Maintenance Therapy Following Autologous Stem Cell Transplantation (ASCT) in Participants with Newly Diagnosed Multiple Myeloma (NDMM)
This project is a Phase III clinical trial sponsored by Celgene (Bristol Myers Squibb/BMS), primarily targeting patients with newly diagnosed multiple myeloma (NDMM). Eligible patients must have received 3 to 6 cycles of prior induction therapy (including a proteasome inhibitor and an immunomodulatory drug), subsequently completed autologous stem cell transplantation (ASCT), and achieved at least a partial response (PR). Patients are randomized to receive maintenance therapy with either the investigational drug Iberdomide (a novel immunomodulatory agent administered for 21 days of each 28-day cycle) or the control drug lenalidomide (a conventional immunomodulatory agent administered continuously in 28-day cycles) until disease progression or unacceptable toxicity. The trial is conducted concurrently across 38 premier centers in China (including Hong Kong and Taiwan)—such as Peking University People's Hospital, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Qilu Hospital of Shandong University—as well as leading international medical centers across 32 countries, including the United States, the United Kingdom, France, Japan, and Australia.
for their academic support:
for myeloma patients globally