In this Q&A, Dr. Akash Khandelwal, Senior Consultant and Head of Department, Hematology, Hemato-Oncology, Bone Marrow Transplant, and CAR-T Cell Therapy at Fortis Hospital, Shalimar Bagh, answers the most common questions patients and families ask about multiple myeloma, from early warning signs to the latest treatment options.
Watch the full conversation:
Q: For someone newly diagnosed with multiple myeloma and no medical background, how would you explain what it actually is?
Multiple myeloma is a unique disease. The problem starts inside the bone marrow but can eventually involve the bones, kidneys, immune system, and other organs. It is a multi-systemic disease, and presentation varies widely from patient to patient. Some people have only bone pain, others only anemia, and some only kidney involvement. By the time most patients reach a clinic, several organs are usually already affected.If someone is dealing with unexplained anemia, unexplained kidney problems, unexplained pain, or unexplained weight loss, that combination warrants evaluation by a hematologist.
Q: What are the early warning signs that patients and families often overlook or mistake for something else? How long does it typically take from symptoms to a confirmed diagnosis?
Multiple myeloma is generally a slow-growing disease. It progresses through stages, starting with plasma cell proliferation, moving into monoclonal gammopathy of undetermined significance (MGUS), then potentially into a smoldering myeloma phase, before becoming active disease. This progression can take years, which makes early identification a challenge.
Common signs that get overlooked include:
- Unexplained bone pain, sometimes misattributed to fractures from age or seen by an orthopedic specialist without deeper investigation
- Unexplained anemia, leading to fatigue, weakness, or recurring blood transfusions
- New-onset kidney problems not clearly linked to any other cause
If kidney involvement is caught early, it is completely salvageable. Patients should not end up on long-term dialysis due to a missed myeloma diagnosis. Recurring, unexplained back pain, consistent weight loss, and new kidney problems are the key signals that call for evaluation.
Q: Why does multiple myeloma make patients so vulnerable to infections?
This comes down to how the disease affects the body's normal design. The plasma cells involved in myeloma are not functioning the way they should. Instead of helping fight infections, they multiply in number without doing their actual job. This is the core reason infection risk rises, both from the disease itself and during treatment, since treatment reduces plasma cell levels further. It is something of a double-edged sword.
Q: What is the connection between myeloma cells and bone destruction? Why do patients experience so much bone pain?
As myeloma cells divide and increase in number, they activate a pathway called RANK ligand, which acts on bone. This activation leads to punched-out lesions, bone breakdown, and osteoporosis. This bone-damaging mechanism is fairly unique to myeloma. It happens because of the way plasma cells behave inside the bone marrow, increasing osteoclast activity and causing lytic lesions.
Q: Not all multiple myeloma cases behave the same way. Some are aggressive while others progress slowly. What determines this?
Genetics play a major role. Some patients are found to have an M-band with no other symptoms, essentially an early or smoldering form of myeloma that can take years to progress. Others have far more aggressive disease, even with treatment.Known high-risk genetic factors include:
- 17p deletion
- Double-hit mutations
- 4;14 and 16-related translocations
- 1q gain or 1q amplification
These features do not favor a good prognosis and are associated with more aggressive disease behavior.
Q: How does risk category affect the treatment plan, and who qualifies for a bone marrow transplant?
Treating multiple myeloma is a marathon. Historically, standard-risk disease was treated less aggressively than high-risk disease. That approach has changed. Even standard-risk patients tend to have better outcomes when treated aggressively upfront.
The current approach is to treat all patients aggressively from the start and consolidate with a bone marrow transplant, regardless of risk category. If a patient's disease continues to behave aggressively despite the best available treatment, that is now considered the true definition of high-risk disease, more so than the risk category alone.
Q: Are bispecific antibodies the treatment of the future for multiple myeloma? How do they work?
Bispecific antibodies are genuinely one of the most exciting developments in myeloma treatment, and they are increasingly being used both post-relapse and, with more data emerging, earlier in treatment as well.
The name comes from having two targets. One target sits on the plasma cell, such as BCMA or GPRC5D. The other target is on immune cells, typically CD3 on T-cells. Currently available options act on both CD3 and BCMA, reducing plasma cell levels significantly and producing very strong responses, including stringent complete remission in some cases. While long-term data is still developing, the results so far are close to what could eventually be described as a cure for myeloma, something previously unheard of.
Q: Who are the ideal candidates for bispecific antibody therapy? Is it for newly diagnosed patients, or only for relapsed disease?
There is not yet enough data to support using bispecific antibodies as first-line treatment for newly diagnosed patients, though that may change with time. Currently, they are used in a relapse setting, particularly first relapse, where they have shown excellent response rates. Two-year progression-free survival in this setting has reached close to 80 to 90 percent, which is exceptionally high for any myeloma treatment seen so far.
Q: Why not just continue chemotherapy indefinitely instead of pursuing a bone marrow transplant?
Relying on the same chemotherapy repeatedly has real limits. No single type of treatment delivers the best possible outcome for multiple myeloma on its own. This is part of why bispecific antibodies represent such a meaningful shift, since they work through a completely different mechanism.
Because myeloma is not curable but a condition that can be controlled, ongoing treatment is required. If transplant or other advanced methods aren't used, the disease tends to return, often more aggressively. The general approach is to combine chemotherapy with daratumumab, follow with an autologous transplant, and continue with maintenance therapy afterward. This combination gives the best results.
Extended chemotherapy use beyond about a year also comes with real downsides, including higher infection risk, neuropathy, weakness, fatigue, and diarrhea, without necessarily improving outcomes. Bone marrow transplant is used specifically to avoid over-relying on chemotherapy alone. It's only skipped when a patient is not medically fit for the procedure.
Q: What is an autologous bone marrow transplant, and why is it used in multiple myeloma?
An autologous transplant offers a way to significantly reduce plasma cells, though it's important to understand that plasma cells cannot be completely eradicated since they are a normal part of the body's system. The goal is disease control.
The process involves first collecting the patient's own stem cells, then using high-dose chemotherapy to eliminate as many remaining plasma cells as possible. Since this chemotherapy also destroys healthy cells, the previously collected stem cells are then re-infused as a rescue mechanism. These typically begin proliferating again within 7 to 10 days. While it doesn't eliminate plasma cells entirely, this approach offers a strong chance of long-term progression-free survival.
Q: What does complete remission mean after a bone marrow transplant? Is the patient cured, or can the disease come back?
About 90 percent of patients will eventually see the disease return, some sooner, some later. The goal of treatment is to push remission out as long as possible and reduce the risk of relapse.
Remission describes the current state, meaning the disease is inactive or undetectable at this point in time. It does not guarantee the disease won't return in six months or a year. A complete remission means plasma cells are not detected. A stringent complete remission means plasma cells were specifically checked for using flow cytometry and were not found. In both cases, this refers to the cancerous plasma cells, not the normal ones the body needs.
Q: What side effects or complications should patients expect during and immediately after a bone marrow transplant?
Because high-dose chemotherapy is used, most of the body's cells are affected, leading to low platelets, low hemoglobin, and reduced immunity. Patients often need blood and platelet transfusions and may require antibiotics if infections develop. Nausea, vomiting, diarrhea, oral ulcers, and hair loss are also common during this phase, which typically lasts around 4 to 5 days before patients start to feel better.
After the transplant, the immune system essentially restarts and functions similarly to a child's immune system for a period, requiring extra caution around public exposure. Around 3 months post-transplant, patients see significant improvement and can resume daily activities. Vaccinations typically begin 6 months post-transplant, and maintenance therapy, usually oral treatment with one or two agents, starts around 3 months post-transplant to help sustain the response.
Q: Is multiple myeloma hereditary? Should family members get tested?
Multiple myeloma is not considered a hereditary disease. However, family members may have a slightly elevated relative risk of developing some form of cancer if there is a family history. It is not a directly transferable or genetic disease in the way some other conditions are.
About Dr. Akash Khandelwal
Dr. Akash Khandelwal is Senior Consultant and Head of the Department of Hematology, Hemato-Oncology, Bone Marrow Transplant, and CAR-T Cell Therapy at Fortis Hospital, Shalimar Bagh, New Delhi. Learn more about his practice and book a consultation with Dr. Akash handelwal.
This article is for informational purposes only and does not constitute medical advice. Please consult a qualified healthcare provider for diagnosis and treatment tailored to your individual condition.
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