At the end of every month, the International Myeloma Foundation Newsroom will feature a wrap-up of some of the most fascinating studies about multiple myeloma from medical journals. Here is our first edition.
The IMF team of medical editors have summarized key findings and conclusions of these studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.
In the Journals (Key Myeloma Research in November 2023)
"Light Chain Multiple Myeloma Presenting As Secondary Cutaneous Amyloidosis: A Case Report on an Uncommon Systemic Manifestation"
Source
Domingos S P, Cabrita B G, Siqueira M S, et al. (November 06, 2023) Light Chain Multiple Myeloma Presenting As Secondary Cutaneous Amyloidosis: A Case Report on an Uncommon Systemic Manifestation. Cureus 15(11): e48346. doi:10.7759/cureus.48346
Description
In this case study, Mrs. Johnson, a 78-year-old woman with a history of high blood pressure, high cholesterol, heart disease, and hemorrhoids. She visited her doctor for rectal bleeding.
About three months ago, Mrs. Johnson visited her doctor and shared that she had been dealing with a condition where her rectum was slipping out (rectal prolapse) and bleeding. However, she didn't want a physical exam because her symptoms got better on their own. She also said no to a colonoscopy. Routine blood tests later revealed she had a mild type of anemia, with low hemoglobin levels at 10.2 g/dL.
This case study revealed an unusual side of multiple myeloma. This type of myeloma usually shows more common signs.
Key Learnings
- Mrs. Johnson's case is not the typical way multiple myeloma shows itself. This makes it challenging for doctors to figure out what's going on.
- Even when things seem a bit strange, doctors need to be really careful and look at all angles. Mrs. Johnson's case demonstrated that it's crucial to work together with different kinds of doctors and always think about what's best for the patient.
- This case is like a reminder for doctors and nurses to stay sharp and always be on the lookout for unexpected signs. It's a fast-changing field and being aware of unusual situations is a must.
In Summary
From the abstract: “In summary, this case calls attention to the importance of documenting atypical presentations and to the dynamic nature of medical practice, urging healthcare professionals to exercise clinical acumen, embrace multidisciplinary collaboration, and remain vigilant for atypical presentations, all while ensuring thorough and patient-centered care.”
"Association Between Synchronous Occurrence of Multiple Myeloma and Carcinoma Prostate: Literature Analysis in the Context of a Case Report."
Source
Kumar Upadhyay A, Kumar M, Kumar A, et al. (November 08, 2023) Association Between Synchronous Occurrence of Multiple Myeloma and Carcinoma Prostate: Literature Analysis in the Context of a Case Report. Cureus 15(11): e48523. doi:10.7759/cureus.48523
Description
In this case study, Mr. Anderson, a 62-year-old man recently visited his doctor due to lower back pain that spread to his left leg over the past three months. His pain got worse in the last month, and he experienced a low-grade fever and significant weight loss of more than 10% in the past six months.
Key Findings
When the doctor checked him, there were no issues with his ability to move or feel things, but he did have some unusual blood results. His white blood cell count was 6.20 × 10^9/L, hemoglobin level was 6.8 g/dL, and platelet count was 151 × 10^9/L. These numbers help the doctor understand what's happening in the body.
More About the Blood Test
Mr. Anderson's blood showed he had 63% neutrophils, 30% lymphocytes, 5% monocytes, 2% eosinophils, and 0% basophils. These are different types of white blood cells that can give clues about health. His red blood cells also seemed a bit off, showing signs of a type of anemia.
The Doctor's Investigation
The doctor did more tests and found that Mr. Anderson had high levels of calcium and creatinine in his blood, which can be a sign of certain health issues. His bone marrow, the soft tissue inside the bones, showed something unusual too—lots of plasma cells, which are a type of blood cell. This pointed toward multiple myeloma.
Putting It All Together
What makes Mr. Anderson's case even more uncommon is that he also had prostate cancer at the same time. Having two different cancers at once is somewhat rare and makes figuring out the right treatment tricky.
Key Learnings
Having both multiple myeloma and prostate cancer together is not something doctors see often.
The doctor did a bone marrow test because they suspected something else might be going on. This emphasizes how crucial it is for doctors to dig deeper when things don't add up.
Managing cases like Mr. Anderson's requires doctors from different specialties to work together. They need to consider a person's overall health, how well their organs are working, and more when deciding on the best treatment.
What's Next?
For Mr. Anderson, the doctor suggests a treatment plan called CyBorD followed by a stem cell transplant. (Learn more about CyBorD here.) This case will likely be helpful for other doctors facing similar challenges, and it also points out the need for more research to understand the link between these two types of cancer better.
Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant
Source
June-Wha Rhee; Raju Pillai; Tianhui He,; et al Alysia Bosworth,; Sitong Chen; Liezl Atencio,; Artem Oganesyan; Kelly Peng; Tati Guzman; Kara Lukas; Brianna Sigala; Aleksi Iukuridze; Lanie Lindenfeld; Faizi Jamal; Pradeep Natarajan; Scott Goldsmith; Amrita Krishnan; Michael Rosenzweig; F. Lennie Wong; Stephen J. Forman; Saro Armenian. Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant. JAMA Cardiol. Published online November 8, 2023. doi:10.1001/jamacardio.2023.4105
Description
In this study, researchers asked: Does a condition called clonal hematopoiesis of indeterminate potential (CHIP) impact the chances of heart problems in individuals with multiple myeloma (MM) after they undergo hematopoietic stem transplant (HCT)?
Findings
In a study of multiple myeloma patients going through HCT, researchers discovered that CHIP was quite common before the transplant, and it linked to a higher risk of cardiovascular disease (CVD) afterward. Specifically, among those with MM and CHIP, more than 20% experienced CVD within five years post-HCT. The risk exceeded 30% for those with both CHIP and factors that could be changed to lower heart risks.
Why It Matters
This discovery suggests that CHIP, identified before HCT, might be a unique sign pointing to potential heart issues in MM patients during and after the transplant.
Objective
The researchers aimed to figure out if there's a connection between CHIP and heart disease in MM patients. They also wanted to explore factors that might change the risk of heart problems for those with CHIP.
Conclusion
The study concluded that CHIP significantly raised the chances of CVD in myeloma patients going through HCT. Even more striking was that those with both CHIP and controllable heart risk factors faced an exceptionally high risk of heart issues. The results propose that CHIP could be a valuable and biologically reasonable marker for predicting heart problems in this group.
What’s Next?
This study calls for more research to see if taking steps to prevent heart issues can lower the risk for multiple myeloma patients with CHIP. Understanding this connection could open doors to better protecting the heart health of individuals facing multiple myeloma and HCT.
"Resolving Therapy Resistance Mechanisms in Multiple Myeloma by Multiomics Subclone Analysis"
Source
Alexandra M. Poos, Nina Prokoph, Moritz J. Przybilla, Jan-Philipp Mallm, Simon Steiger, Isabelle Seufert, Lukas John, Stephan M. Tirier, Katharina Bauer, Anja Baumann, Jennifer Rohleder, Umair Munawar, Leo Rasche, K. Martin Kortüm, Nicola Giesen, Philipp Reichert, Stefanie Huhn, Carsten Müller-Tidow, Hartmut Goldschmidt, Oliver Stegle, Marc S. Raab, Karsten Rippe, Niels Weinhold. Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis. Blood (2023) 142 (19): 1633–1646. https://doi.org/10.1182/blood.2023019758. Published November 9, 2023.
Key Points
- The study uncovers hidden challenges in treating multiple myeloma, showing that different resistance mechanisms can work together.
- The researchers explored how specific groups of myeloma cells interact with the bone marrow environment, creating a complex puzzle of resistance.
Overview
When treating multiple myeloma, some patients develop resistance to treatments over time.
The study looked at 15 patients with multiple myeloma who faced challenges after trying different treatments. Using advanced techniques like whole-genome sequencing and single-cell analysis, researchers looked closely at their cancer cells over time.
Key Learnings
- Certain groups of cells had resistance built into their genes even before treatment started. It's like they had a plan to survive.
- Different cell groups, though genetically unique, started acting similarly, adapting together to resist treatment (as if they were having sharing strategies).
- Myeloma cells didn't fight alone. They teamed up with cells in the bone marrow, creating a challenging environment for treatments.
Why It Matters
Understanding these microscopic battles helps us see the bigger picture of why some myeloma patients struggle with treatment. It's like decoding a secret language that cancer cells use to survive.
What’s Next?
This study sets the stage for future research. By tracking these resistant cell groups, researchers hope to find new targets for treatments. It's like finding the weak points in a fortress to make these therapies more effective against stubborn myeloma cells.
"Genomic and Immune Signatures Predict Clinical Outcome in Newly Diagnosed Multiple Myeloma with Immunotherapy"
Source
Maura, F., Boyle, E.M., Coffey, D. et al. Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens. Nat Cancer (2023). https://doi.org/10.1038/s43018-023-00657-1 Published November 9, 2023.
Overview
Darzalex (daratumumab) has a big impact as a treatment for multiple myeloma. Despite improvements, about 40% of patients don't respond as expected.
Key Findings
- The study looked at the genetic makeup of tumors and the tiny world around them in patients using a treatment combination (carfilzomib, lenalidomide, dexamethasone, and daratumumab).
- Certain genetic traits in the tumors, like high APOBEC mutational activity, deletions of IKZF3 and RPL5, and a gain of 8q, played a role in how well patients responded to treatment.
- Checking bone marrow profiles before and after treatment cycles revealed some interesting patterns. The number of natural killer cells and T cell diversity before treatment, along with changes in immune activity over time, could predict how well the treatment worked.
Why It Matters
Understanding these genetic and immune system clues helps doctors predict how a patient will respond to treatment. It's like having a roadmap to tailor treatments for each individual, making them more effective.
Conclusion
From the abstract: “Overall, this study provides strong evidence of a complex interplay between tumor cells and the immune microenvironment that is predictive of clinical outcome and depth of treatment response in patients with newly diagnosed multiple myeloma treated with highly effective combinations containing anti-CD38 antibodies.” This study is just the beginning. By untangling the complexity between cancer cells and the immune system, researchers are finding smarter, more personalized treatments for those with multiple myeloma.
"Concomitant 1q+ and t(4;14) Influences Disease Characteristics, Immune System, an Prognosis in Double-Hit Multiple Myeloma"
Source
Ozga, M., Zhao, Q., Huric, L. et al. Concomitant 1q+ and t(4;14) influences disease characteristics, immune system, and prognosis in double-hit multiple myeloma. Blood Cancer J. 13, 167 (2023). https://doi.org/10.1038/s41408-023-00943-2. Published November 10, 2023.
Key Findings
In this study, specific genetic markers, like 1q+ and t(4;14), and how they impact the prognosis of patients were investigated. When assessing the effects of certain treatments, like autologous stem cell transplant (ASCT), it's crucial to consider the size of these genetic markers.
Within this exploration, researchers identified a subgroup of patients with a combination of 1q+ and t(4;14), termed as DH. These patients, usually younger, showed different characteristics and responded less positively to ASCT. The difference in response seems linked to changes in the expression of certain genes and immune populations.
Researchers looked at specific locations and patterns of the 1q+ marker. Notably, they found that 1q23+ alone and larger gains of chromosome 1 were associated with poorer outcomes. Using multiple probes for 1q+ analysis could help better understand and classify patients.
Limitations of the Study and Future Outlook
The study has some limitations, like focusing only on patients with specific genetic markers. More research is needed to compare these patients with those who have standard-risk multiple myeloma. Additionally, the analysis of immune cells was limited, and further investigation is needed to set standards for sample purity. As technology evolves, researchers hope to explore how newer methods, such as next-generation sequencing, can enhance our understanding of genetic variations.
Conclusion
The study sparks important questions about predicting outcomes in multiple myeloma. From the study: “In conclusion, our study raises important questions in the field of 1q+/t(4;14) prognostication: 1. Is there a need to uniformily define CA cutoffs?; 2. Should we use multiple 1q probes?; 3. Are we ready to use these CAs as predictive markers of response? Answering these questions will improve estimation of risk and impact therapeutic choices in patients with MM.”
"National Comprehensive Cancer Network Guideline Recommendations of Cancer Drugs with Accelerated Approval."
Source
Cliff ERS, Rome RS, Kesselheim AS, Rome BN. National Comprehensive Cancer Network guideline recommendations of cancer drugs with accelerated approval. JAMA Netw Open. Published online November 14, 2023. doi:10.1001/jamanetworkopen.2023.43285
The Study’s Question
How does the approval process impact the guidelines for cancer drugs in the National Comprehensive Cancer Network (NCCN)?
Key Findings
In a study examining 315 cancer indications for 100 drugs, it was discovered that cancer drugs approved through the US Food and Drug Administration (FDA) accelerated pathway received lower ratings in the NCCN guidelines compared to those approved through the regular process.
What It Means
The study suggests that there's a need for stronger evidence in guiding decisions for cancer treatment. It also highlights the importance of clearer criteria for evidence in the NCCN guidelines, making them more helpful for doctors, patients, and those responsible for covering treatment costs.
In the world of cancer treatment, understanding how drugs get approved is crucial. A recent study focused on cancer drugs approved through the U.S. FDA's accelerated process and how they are assessed in the NCCN guidelines, which doctors commonly use for guidance.
More Details About This Study
- Researchers looked at 315 cancer indications for 100 drugs, exploring how they were approved by the FDA—whether through the accelerated pathway or the regular process.
- Drugs with accelerated approval tended to have lower ratings in the NCCN guidelines compared to those with regular approval. This means that the evidence supporting these drugs in the accelerated pathway was seen as less robust.
Why It Matters
When it comes to treating cancer, having clear guidelines is essential. The study suggests that more solid evidence is needed to guide decisions, ensuring that the best treatments are chosen for patients. Clearer guidelines can benefit doctors, patients, and those involved in covering treatment costs.
"Challenging Diagnosis of Lytic Bone Lesions Between Multiple Myeloma and Bone Metastasis of Primary Breast Cancer"
Source
Edahiro T, Ureshino H, Yoshida T, et al. (November 16, 2023) Challenging Diagnosis of Lytic Bone Lesions Between Multiple Myeloma and Bone Metastasis of Primary Breast Cancer. Cureus 15(11): e48880. doi:10.7759/cureus.48880
About the Case Study
Breast cancer, a common diagnosis in women, can sometimes spread to the bones, causing lytic lesions—a condition where bones break down. While these lesions usually point to metastatic breast cancer, they can be misleading. This case study presents a unique case where primary breast cancer mimicked bone metastasis but turned out to be multiple myeloma.
Case Presentation
A 47-year-old woman with a previous breast cancer diagnosis visited ahematology department. Initially, her breast cancer was identified through a biopsy, and imaging scans revealed bone lesions, suggesting widespread bone metastases. She started treatment for breast cancer, but after six months, despite improvements in the breast, the bone lesions worsened.
Diagnosing the cause of bone lesions is complex. Standard imaging methods like MRI or PET-CT scans can be inconclusive. In this case, the situation was further complicated by the coexistence of primary breast cancer and multiple myeloma.
Key Learnings
Amidst the complexity, a noninvasive method—urinalysis—played a crucial role. By evaluating urine protein levels, doctors gained valuable diagnostic information. This simple test can be a game-changer in cases where bone lesions pose a diagnostic challenge.
Conclusion
From the abstract: “The diagnosis of lytic bone lesions is challenging. A standard imaging method including MRI or FDG PET-CT has not been established. We recommend that physicians should evaluate urine protein levels when lytic bone lesions are noted because urinalysis is a noninvasive evaluation method that includes useful diagnostic information. The evaluation of the M-protein is valuable in diagnosing multiple myeloma.”
"Anti-TACI Single and Dual-Targeting CAR T Cells Overcome BCMA Antigen Loss in Multiple Myeloma"
Source
Larson, R.C., Kann, M.C., Graham, C. et al. Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma. Nat Commun 14, 7509 (2023). https://doi.org/10.1038/s41467-023-43416-7. November 18, 2023.
About the Study
In multiple myeloma treatment, Chimeric Antigen Receptor (CAR) T cells have shown promise, but challenges remain. Some patients don't achieve lasting remissions, and there's a risk of severe side effects. This study introduces a fresh approach using CAR T cells targeting a protein called TACI alongside the conventional target, BCMA. This dual-target strategy aims to enhance effectiveness while potentially minimizing certain side effects.
Discussion
CAR T cell therapy targeting BCMA has been successful, but some patients relapse with BCMA-negative disease, posing a significant hurdle. To address this, the study explores TACI as an additional target, a protein highly expressed in multiple myeloma. Unlike other attempts using natural ligands, this study develops CARs using a novel approach, showing promising results.
Key Findings
- CAR T cells designed against TACI exhibit robust anti-tumor activity in laboratory tests and animal models, hinting at their potential in treating multiple myeloma.
- TACI, when targeted alone, could be a safer alternative with fewer potential side effects in the brain, compared to strategies solely focusing on increasing BCMA binding.
- Dual-specific CAR T cells targeting both BCMA and TACI simultaneously demonstrate superior efficacy in some scenarios, offering a potential solution to antigen escape issues.
Conclusion
From the abstract: “In conclusion, we report potent anti-tumor activity of monospecific anti-TACI and bispecific anti-BCMA–anti-TACI CAR T cells in vitro and in xenograft models of multiple myeloma. These CAR T cells could offer an additional therapeutic option for patients with multiple myeloma or other plasma cell disorders.”
"Skin Rash as a Side Effect of Bortezomib: A Case Report"
Source
Khaldy M, Hamdan S, Amar M, et al. (November 19, 2023) Skin Rash as a Side Effect of Bortezomib: A Case Report. Cureus 15(11): e49051. doi:10.7759/cureus.49051
About the Study
Bortezomib, a drug that is key in treating multiple myeloma, sometimes brings unexpected challenges. Commonly causing nausea and neuropathic pain, it can also trigger rare side effects like skin rash. In this case, a 72-year-old woman with a history of multiple myeloma experienced a distinctive skin reaction during bortezomib treatment. Despite its uncommon occurrence, understanding and identifying such reactions are crucial for timely intervention.
About Velcade (bortezomib)
Bortezomib, introduced in 2003, revolutionized multiple myeloma treatment. Given in combinations like VRd protocol, it yields positive outcomes. However, it isn't without issues. Skin reactions, though rare (10-24%), can occur. This case explores an elderly patient's journey with bortezomib and the unexpected twist involving a skin rash.
Key Learnings
- The patient, battling multiple myeloma, underwent various protocols, including VTD and Vd. In May 2023, a change to VRd protocol was made due to disease progression.
- In August 2023, the patient developed an itchy, raised skin rash, starting in the palms and soles and spreading. This occurrence, 21 months into treatment, raised concerns.
- The patient, seeking help for weakness and numbness, highlighted the skin rash linked to bortezomib. With low blood pressure and oxygen levels, prompt attention was crucial.
- The skin rash, confirmed via biopsy, unveiled a rare bortezomib-induced reaction. Surprisingly, it surfaced long after treatment initiation. This challenges the notion that such reactions appear early, urging clinicians to remain vigilant throughout the treatment course.
Conclusion
From the abstract: “Bortezomib-induced skin rash has been reported in 15% of patients, with the onset being mostly following the second cycle of treatment. In this case, we report a patient with an erythematous skin rash that appeared 21 months after the first exposure to bortezomib. It was confirmed with histopathological findings of perivascular lymphocytic infiltrations on skin biopsy. Based on that, bortezomib-induced skin rash should be suspected in patients with new-onset skin rash even if they have been on treatment for a long time. We recommend keeping it in the differential diagnosis of patients on maintenance bortezomib.”