Radiation Therapy for Multiple Myeloma

Overseen By Penny Fang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Other malignancy, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of radiation therapy for individuals with multiple myeloma, a type of blood cancer, who have undergone BCMA CAR-T cell therapy but still exhibit active disease. It targets specific cancer spots in bones or soft tissues. Participants must have had a PET scan showing active disease at least 30 days after their CAR-T treatment and possess a myeloma lesion suitable for radiation targeting. The trial evaluates patient response to radiation treatment and the duration of that response. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this radiation therapy is safe for treating multiple myeloma?

Research has shown that radiation therapy is generally safe and effective for many types of cancer treatments. Studies have found that patients can safely receive radiation therapy alongside other treatments, such as biological agents, allowing these therapies to work together. Radiation therapy targets tumors with strong doses, helping to protect the surrounding healthy tissue.

In this trial, radiation therapy treats specific areas affected by multiple myeloma, such as bony or soft tissue growths called plasmacytomas. While all medical treatments can have side effects, this method focuses on the cancer itself, potentially reducing unwanted effects on other parts of the body. Overall, past studies suggest that patients often tolerate this type of treatment well, making it a promising option for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Radiation therapy for multiple myeloma is unique because it targets specific areas affected by the disease, like bony or soft tissue plasmacytomas, with a concentrated dose of radiation. Unlike traditional treatments such as chemotherapy or systemic drug therapies, which affect the whole body, this approach focuses on localized sites, potentially reducing side effects. Researchers are excited about this treatment because it may offer quicker relief of symptoms and can be tailored to the patient's specific needs, providing a more personalized treatment option.

What evidence suggests that radiation therapy might be an effective treatment for multiple myeloma?

Research has shown that radiation therapy, which participants in this trial will receive, can help treat multiple myeloma, a type of blood cancer. Studies have found that many patients experience significantly less pain after radiation, with about 92% reporting reduced pain and 66% achieving complete pain relief. Another study discovered that radiation can quickly and effectively relieve symptoms from spinal myeloma lesions. Specifically, patients in that study demonstrated complete or partial improvement when treated with radiation, indicating its potential to control the disease. These findings suggest that radiation therapy can be a promising option for managing symptoms and possibly slowing the disease's progression in people with multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

Penny Fang, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed refractory multiple myeloma (RRMM) who have had standard BCMA CAR-T cell therapy but still show active disease on scans. They must be able to consent and have at least one treatable myeloma lesion. Pregnant women or those planning chemotherapy within two weeks of radiation are excluded.

Inclusion Criteria

My scan 30 days after CAR-T therapy shows the cancer is still active.

I have been diagnosed with multiple myeloma.

I have a myeloma lesion treatable with radiation.

Exclusion Criteria

Pregnant women will be excluded from this study.

I am scheduled for chemotherapy within 2 weeks after finishing radiation.

I am currently being treated for a cancer that is not multiple myeloma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Radiation treatment to bony or soft tissue plasmacytomas in up to five fields with doses of 10-20Gy

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after radiation treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy

Trial Overview The study tests the safety and effectiveness of salvage radiation treatment after BCMA CAR-T therapy in patients with RRMM. Up to five areas can receive radiation, with doses adjusted by the physician. The main goals are to see how many respond to treatment and how long their response lasts.

How Is the Trial Designed?

Group I: Radiation Therapy Experimental Treatment 1 Intervention

Radiation treatment will be to bony or soft tissue plasmacytomas in up to five radiation treatment fields to 10-20Gy (or equivalent dose in 2Gy fractions of 10-21Gy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

Radiation therapy (RT) is still an important treatment for multiple myeloma (MM), used in 34% of patients primarily for pain relief and prevention of complications like fractures, even in the era of new therapies.

RT effectively alleviates pain in MM patients, with 76.4% achieving complete pain relief, and it does not negatively impact the collection of stem cells for autologous stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current role of radiation therapy for multiple myeloma. Talamo, G., Dimaio, C., Abbi, KK., et al.[2022]

Intraoperative radiation therapy (IORT) allows for targeted radiation delivery during surgery, which can enhance local control of tumors while minimizing damage to surrounding healthy tissues, making it particularly beneficial for patients with locally advanced or recurrent cancers.

The addition of IORT to standard treatment regimens has shown improved local control and survival rates in various cancers, including rectal cancer and breast cancer, suggesting its potential for broader application in clinical practice as new, cost-effective devices become available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative radiation therapy. Willett, CG., Czito, BG., Tyler, DS.[2022]

Intraoperative radiotherapy (IORT) was used in a study involving 1367 patients with 1400 tumors, showing a 5-year local recurrence rate of 5.98% for those receiving IORT only, which is comparable to other IORT studies but higher than standard whole breast radiation therapy (WBRT).

IORT offers benefits such as convenience and low complication rates, making it a viable option for patients meeting specific criteria, although the addition of WBRT was found to significantly reduce the risk of local recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). Silverstein, MJ., Epstein, MS., Chen, P., et al.[2022]

Intraoperative radiotherapy (IORT) as a tumor bed boost in breast-conserving surgery showed promising safety and efficacy, with only 8% of patients experiencing acute grade 3 toxicities and no grade 4 events reported among 214 patients followed for a median of 28 months.

The study found a low recurrence rate, with only two cases of tumor bed recurrence and one contralateral breast event, suggesting that IORT may effectively reduce the risk of local progression in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy boost as part of breast-conservation therapy for breast cancer: a single-institution retrospective analysis. Stoian, R., Erbes, T., Zamboglou, C., et al.[2022]

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

Radiotherapy is effective but carries specific safety risks due to the high doses of radiation used, making human oversight crucial for safe practice.

A systematic approach to prevent accidental exposures in radiotherapy is recommended, including assigning responsibilities, learning from past incidents, and proactively identifying potential hazards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tools for risk assessment in radiation therapy. Ortiz López, P.[2019]

In a study of 29 patients with multiple myeloma, radiation therapy provided significant symptomatic relief, achieving remission in 92% of painful lesions and 75% of neurological abnormalities, indicating its effectiveness as a palliative treatment.

The study suggests that higher total radiation doses (median 40 Gy) may be necessary for adequate pain relief, with complete relief observed at a median total dose of 66 Gy, which is higher than the previously reported effective range of 10 to 20 Gy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Palliative radiation therapy for multiple myeloma]. Minowa, Y., Sasai, K., Ishigaki, T., et al.[2011]

Intraoperative radiotherapy (IORT) allows for the precise delivery of high doses of radiation directly to tumors during surgery, improving the therapeutic ratio by maximizing tumor dose while minimizing exposure to surrounding healthy tissues.

IORT has shown efficacy in treating various cancers, including early-stage breast cancer and recurrent tumors, and has become more accessible due to advancements in technology, such as mobile linear accelerators and low-kV devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy: review of techniques and results. Pilar, A., Gupta, M., Ghosh Laskar, S., et al.[2020]

In a study of 3011 patients with multiple myeloma, 30% received radiation therapy (RT), which was notably associated with factors like performance status, disease stage, and the presence of bone lesions or severe osteoporosis, indicating its targeted use for symptom relief.

RT is frequently utilized in the later stages of multiple myeloma, particularly for palliative care, as patients approach the end of life and have fewer treatment options available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Utilization of Radiation Therapy in Multiple Myeloma: An Analysis of the Connect® MM Registry. Ballas, L., Ailawadhi, S., Narang, M., et al.[2023]

In a study of 46 multiple myeloma patients, a single fraction of 8 Gy radiotherapy effectively reduced pain in 78.3% of cases, with 43.5% experiencing complete pain relief.

The treatment also promoted bone recalcification in 55% of patients, with manageable side effects that were mostly mild and reversible, indicating its safety and efficacy in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of one fraction of 8 Gy radiotherapy in palliative treatment of multiple myeloma patients with painful bone destructions. Rudzianskiene, M., Inciura, A., Juozaityte, E., et al.[2022]

In a study of 127 multiple myeloma patients undergoing conventional external beam radiation therapy, 30.7% experienced new or worsened vertebral compression fractures (VCFs) within 3 years, affecting 11.2% of the treated vertebrae.

The Spinal Instability Neoplastic Score (SINS) was found to be a reliable predictor of VCFs, with higher scores correlating with increased fracture rates, while the use of bisphosphonates was associated with a reduced risk of new or progressed VCFs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fracture rate after conventional external beam radiation therapy to the spine in multiple myeloma patients. Te Velde, JP., Zijlstra, H., Lans, A., et al.[2023]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

In a study of 80 head and neck rhabdomyosarcoma (HNRMS) survivors with a median follow-up of 10.5 years, 63% experienced at least one severe adverse event (AE), and 76% had five or more AEs, highlighting the significant impact of treatment-related complications.

Survivors treated with the innovative AMORE approach had a lower risk of severe AEs compared to those treated with standard external beam radiotherapy (EBRT), while overall survival rates were similar between the two groups, suggesting that AMORE may be a safer alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment. Schoot, RA., Slater, O., Ronckers, CM., et al.[2015]

Intraoperative radiotherapy (IORT) for early-stage breast cancer significantly improves radiation-related quality of life (QoL) parameters, with patients reporting less pain and better functioning compared to those receiving external beam radiotherapy (EBRT).

In a study of 230 women, those treated with IORT alone experienced fewer breast and arm symptoms and better overall role functioning, indicating that IORT may be a more patient-friendly option than traditional EBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. Welzel, G., Boch, A., Sperk, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4332323/

Current Role of Radiation Therapy for Multiple Myeloma The median biological effective dose (BED) was 37.5, 36, and 39 Gy in patients with complete response, partial response, and stable pain level, respectively, ...

2. link.springer.com link.springer.com/article/10.1007/s00066-024-02198-7

Excellent long-term pain response and local control ... Overall, 92% of patients reported reduced pain after radiotherapy, with 66% reporting complete pain response.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5024659/

Excellent outcomes after radiotherapy alone for malignant ... Data of 238 patients presenting with motor deficits of the lower extremities in consequence of SCC from vertebral body myeloma were retrospectively analyzed.

4. thejns.org thejns.org/spine/view/journals/j-neurosurg-spine/26/3/article-p282.xml

Spine stereotactic radiosurgery for the treatment of multiple ... This study reports the largest series of myeloma lesions treated with spine SRS. A rapid and durable symptomatic response was observed, with a median time to ...

5. haematologica.org haematologica.org/article/view/9958

New paradigm for radiation in multiple myeloma: lower yet ... We report here a large number of patients treated with radiation at a single institution for plasmacytoma over a period of nearly two decades.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3986382/

Stereotactic Body Radiation Therapy Versus Intensity ... Although SBRT was associated with lower treatment costs, there appears to be a greater rate of GU toxicity for patients undergoing SBRT compared with IMRT.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6349658/

The Safety Profile of Concurrent Therapy for Multiple ... Our study found that that patients can safely receive palliative radiation therapy while on biological agents.

8. businesswire.com businesswire.com/news/home/20251029078394/en/European-Commission-Approves-KEYTRUDA-pembrolizumab-as-Part-of-a-Treatment-Regimen-for-Adults-with-Resectable-Locally-Advanced-Head-and-Neck-Squamous-Cell-Carcinoma-LA-HNSCC-Expressing-PD-L1-CPS-1

European Commission Approves KEYTRUDA ... Increased Mortality in Patients With Multiple Myeloma. In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide ...

9. cinj.org cinj.org/patient-care/stereotactic-body-radiotherapy-sbrt

Stereotactic Body Radiotherapy - SBRT Stereotactic radiotherapy destroys tumors with precise, very intense doses of radiation while limiting damage to healthy tissue.

10. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2835449

Therapy, Safety, and Logistics of Preoperative vs ... Preoperative SRT was safe and logistically feasible with the potential benefit of expediting treatment.