Prerna Mewawalla, MD, is medical director of Apheresis and a hematologist-oncologist in the Division of Hematology and Cellular Therapy at Allegheny Health Network, as well as an associate professor at the Drexel University College of Medicine in Pennsylvania.

Prerna Mewawalla, MD, discusses needs that remain to be addressed in patients with relapsed/refractory myeloma who receive earlier-line CAR T-cell therapy.

Dr Mewawalla on Unmet Needs After Early CAR T-Cell Therapy in Relapsed/Refractory Myeloma

“Our current salvage options and sequencing after using early CAR T-cell therapy are not clearly defined. Do we go to bispecific [antibodies] later? Do we go to our traditional regimens after? This truly needs to be defined after early CAR T-cell therapy.”

Prerna Mewawalla, MD, medical director of Apheresis and a hematologist-oncologist in the Division of Hematology and Cellular Therapy at Allegheny Health Network, as well as an associate professor at the Drexel University College of Medicine, discussed unmet needs and questions that emerge following earlier lines of CAR T-cell therapy for the treatment of patients with relapsed/refractory multiple myeloma.

 (Carvykti) for the treatment of patients with relapsed/refractory multiple myeloma who have previously received at least 1 line of therapy—including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD)—and who are refractory to lenalidomide (Revlimid). At the same time, 

the FDA also approved idecabtagene vicleucel

 (Abecma) for the treatment of patients with relapsed/refractory multiple myeloma who have been treated with at least 2 prior lines of therapies, including a PI, an IMiD, and an anti-CD38 monoclonal antibody.

There are several questions that have yet to be addressed regarding further disease management after earlier lines of CAR T-cell therapy in patients with relapsed/refractory multiple myeloma, Mewawalla began. She noted that current salvage options and sequencing strategies after early CAR T-cell therapy are still undefined. Questions include whether bispecific antibodies and traditional regimens should be used following early CAR T-cell therapy, she added.

Furthermore, trials are evaluating whether maintenance therapy is required after CAR T-cell therapies, and whether this could affect patients’ chances of achieving durable responses is another currently unanswered question, Mewawalla stated. The scaling up of CAR T-cell therapy access to meet the growing demand is another unmet need, she explained. CAR T-cell therapies are intensive treatments, and infusion center infrastructure may further limit how many patients can receive these treatments, revealing another disparity, particularly for patients who are eligible but live far away from academic centers or transplant sites, she concluded.

Videos

Prerna Mewawalla, MD, explains the roles of cilta-cel and ide-cel in clinical practice for the treatment of relapsed/refractory multiple myeloma.

Dr Mewawalla on the Real-World Roles of Cilta-Cel and Ide-Cel in R/R Myeloma 

“[The April 2024 FDA approvals of cilta-cel and ide-cel] moved CAR T-cell therapy into earlier lines. In earlier lines, patients have better T cell fitness, and their diseases are also better controlled. Therefore, this is going to redefine the standard of care at first relapse for high-risk patients [with multiple myeloma].”

Prerna Mewawalla, MD, medical director of Apheresis and a hematologist-oncologist in the Division of Hematology and Cellular Therapy at Allegheny Health Network, as well as an associate professor at the Drexel University College of Medicine, explained what the April 2024 FDA approvals of ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) for the treatment of relapsed/refractory multiple myeloma now mean for clinical practice.

 for the treatment of patients with relapsed/refractory multiple myeloma who were treated with at least 1 prior line of therapy, which included a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and who are refractory to lenalidomide (Revlimid). The same day, 

 for the treatment of patients with relapsed/refractory multiple myeloma who previously received at least 2 therapies, including a PI, IMiD, and an anti-CD38 monoclonal antibody.

Previously, CAR T-cell therapies were options in later lines of therapy, with both ide-cel and cilta-cel initially approved after 4 or more prior treatment lines; however, these 2 expanded approvals shifted the narrative, and CAR T-cell therapies are no longer the last option for patients with relapsed/refractory multiple myeloma, Mewawalla began. With cilta-cel and ide-cel now indicated in earlier lines of therapy, patients at this stage in treatment tend to have better T-cell fitness, and their disease is more controlled, she explained. Although this is still new in clinical practice, she noted that this could help redefine the standard of care for high-risk patients at first relapse. Additionally, it promotes reevaluation of post–CAR T-cell therapy strategies, as it has historically been used in later lines, she added. As CAR T-cell therapy is used in earlier lines of therapy, it’s important to consider what treatments are available as subsequent treatment, Mewawalla concluded.

 every time we needed to look up information on a medication? More often than not, we had to run down to the nearest desktop computer in the hospital or university to browse through information, or at times visit the neighborhood library. Now, there are thousands of medical mobile applications that can provide quick access to information.

	So why is it necessary for hematology and oncology fellows to know more about mobile apps? Life as a fellow is extremely hectic, and mobile apps can help us save an enormous amount of time when conducting research. These apps can also help us become more efficient. However, they should all be regarded as accessories.

	For the medical fraternity, life has just become more efficient, more accurate, and much faster—all we need to know about medicine is literally at our fingertips.

	When you use a mobile app on your smartphone, lo and behold, everything you want to know appears instantaneously. We now have the opportunity to access information while sitting with patients, rounding, and moving from one floor to another. However, in this information age, there is an abundance of information that can make it difficult to access the most pertinent and reliable medical information. Therefore, I have developed this article to help you understand which types of mobile apps may be most useful during fellowship, as well as throughout your medical career.

	As a hematology-oncology fellow, I find medical calculation apps like MediCal extremely useful. These apps perform several types of important calculations (eg, 4T score, carboplatin dosing). They are also very helpful in grading patients’ performance statuses and when staging diseases like myelodysplastic syndrome with the International Prognostic Scoring System.

	When managing care for my cancer patients, I like to refer to the NCCN Guidelines and UpToDate apps on my phone. These apps help me make reliable and fast decisions about how to treat and care for my patients.

	And because memorizing steroid and opioid conversions can be so difficult, yet so important to understand and perform correctly when treating patients, I like to use apps such as CortiConverter and Opioid Converter. Making errors when converting drugs from one type to another can lead to serious issues such as opioid overdose.

	In addition, several mobile apps now help patients better collaborate with their cancer care team. When used correctly, patient-friendly mobile apps can make it easier to review enormous amounts of patient data related to their diagnosis, treatment options, outcomes, and survivorship issues, and can help us make more informed decisions.

	Apple recently launched ResearchKit, which enables medical research in real time. Patients choose to submit their health parameters in a predefined format using specific apps on their smartphones. ResearchKit is expected to help professionals access important patient-related health data that can make it easier to deliver more personalized care to their patients. High-value and insightful patient data, so hard and tedious to collect in the past, is now readily available to us.

	When suggesting patient-friendly mobile apps to your patients, it is important to remember that they have a strong say in sharing only the data they are most comfortable sharing, as protected by the Health Insurance Portability and Accountability Act. However, patient-friendly apps are extremely useful and have the potential to enrich the research that has been primarily survey-based in the past.

	Some applications, although not designed specifically for use in the medical world, still go a long way in providing medical-related servi-ces and support. For instance, I use Genuis Scan to create a snapshots of important documents. These snapshots can quickly be converted into PDFs or JPEG files and shared instantaneously.

	I also find the Fax Burner mobile app helpful. Fax Burner makes it possible to send and receive faxes right from your smartphone. Isn’t it fascinating that a phone in the palm of your hand can replace a 20-pound facsimile machine?

	As a fellow, it can be difficult sifting through the most recent and important medical articles and keeping up-to-date on cancer research. However, I find mobile apps such as Evernote, Slack, and BaseCamp helpful when reading up on or sharing the latest in oncology, and when collaborating with colleagues.

	During fellowship, storage and quick retrieval of important medical articles you access often is essential. I find apps like iBooks and Pocket helpful for storing, sharing, and referring back to articles of interest.

	Additionally, Cloud Storage—free for limited use&mdash;provides access to this information on-the-go on all mobile devices, and across all geographies. Our call schedules, lecture schedules, notes, pictures, and even Doodle are available on the go.

	Dropbox, OneDrive, and Google Drive have almost eliminated the need for CD/DVDs, pen drives, and even hard disks. You need not be tethered to a desktop anymore. Apps such as File Manager work like a pen drive, enabling you to store any type of document for access at a later time.

	This is just the beginning. With the “smart wearable” market exploding, technology like smartwatches, JawBone, or FitBit bands further help us navigate through our busy day. But can using all these applications make us dumber? Over time, will we forget doses, formulae, and chemotherapy regimens? Are we too dependent on these electronic tools? 

	I recently read a study that examined the smartphone addiction. A survey of 1600 managers and professionals by Leslie Perlow, PhD, the Konosuke Matsushita professor of leadership at Harvard Business School, found that:

		70% check their smartphones within an hour of getting up; 

		56% check their phone within an hour of going to sleep; 

		48% check over the weekend, including Friday and Saturday nights;

		51% check continuously during vacations;

		44% said they would experience “a great deal of anxiety” if they lost their phone and couldn’t replace it for a week. 

	It is very important to maintain a good balance when using all the new technology available at our fingertips. We should NOT lose our knowledge base, especially when providing care to our patients. We should use technology as an accessory but not rely on it to make all our decisions. 

	Mobile Medicine: Apps for the Healthcare Professional

	Endorsed by the End-of-Life Nursing Education Consortium and renowned palliative care physician Diane Meier, the Health Communication app provides access to theory-driven and evidence-based communication tools that are useful in difficult conversations with patients during moments of tension, sorrow, fear, anxiety, awkwardness, and hesitancy. Health Communication provides over 100 different communication strategies (searchable by scenario) to help clinicians provide compassionate and culturally sensitive care to seriously and critically-ill patients and their families. 

	The American Society of Clinical Oncology’s Cancer.net Mobile app provides accurate, oncologist-approved cancer information on 120 types of cancer including information about treating cancer, managing side effects, managing the cost of care, and living with cancer. Healthcare professionals can suggest this app to their patients to help them save information about their prescribed medications, including photos of labels and bottles, and track the time and severity of symptoms and side effects. 

: Free download preview; $39.99 in-app purchase

: Android, BlackBerry, iPhone, iPad, and iPod touch 

	The Pocket Guide to Diagnostic Tests app can be used by healthcare professionals who need to review accurate recommendations for ordering and interpreting laboratory, diagnostic, and imaging tests. This app provides immediate, evidence-based information on the selection and interpretation of more than 450 commonly used laboratory and electrocardiographic tests, diagnostic imaging tests, and therapeutic monitoring tests. Additional features include a universal index search tool to help professionals quickly locate information and a “Favorites” tool for bookmarking important entries. 

	Docphin is designed to help busy healthcare professionals keep up with the latest in medical research. Currently trusted by medical professionals in over 400 hospitals in more than 15 countries, this app allows users to create a personalized medical newsfeed and receive alerts when their favorite medical journals publish articles on specified medical topics or by particular authors. With Docphin, users can access full-article PDFs, save them, and e-mail them to colleagues. 

	My Cancer Genome is designed to help medical professionals keep track of the rapidly evolving world of genetically informed cancer medicine. App users can search for and save information on cancer types, cancer-related genes, and specific cancer-related genetic mutations. The app also provides information on drug classes, drug targets, and drug names for antineoplastic agents, either FDA-approved or being studied in clinical trials. 

	1. Breaking the smartphone addiction. Harvard Business School website. 

. Published May 14, 2012. Accessed May 7, 2015. 

Articles

Life as a fellow is extremely hectic, and mobile apps can help us save an enormous amount of time when conducting research.

Smart Apps for Smart Docs

			A Korean patient within my clinic was diagnosed with high-risk myelodysplastic syndrome. Stem cell transplant was the only chance for cure. Unfortunately, her sibling wasn’t a match, and no matches were located in the American donor registry either. There were 2 matches found in the Asian donor registry, but both were unavailable.

			A recent media article described a woman of Indian descent with leukemia who could not find a donor for a life-saving bone marrow transplant.

In the instance of the first patient, the search for a donor continues. In the instance of the second, the tragedy of this woman’s death could have very well been averted.

	What are stem cell transplants and when are they used?

Hematopoietic stem cell transplantation (HSCT) is a procedure performed to help restore hematopoietic stem cells, cells that normally divide or mature into white or red blood cells, and platelets that have been destroyed by chemotherapy or radiation treatment. HSCT is performed most commonly for certain types of blood and bone marrow cancers. To restore the cells, the procedure includes the use of peripheral blood, bone marrow, or umbilical cord tissue.

 For certain types of cancer, it is the only hope for cure. Unlike patients undergoing solid organ transplants, those undergoing HSCT have to be matched for DNA, specifically for human leukocyte antigen (HLA) types on chromosome 6.

	The relationship between ethnicity and available donor matches

Historically, it has been observed that patients are more likely to match their HLA type with another person within the same ethnic group. The number of HLA types seen among one ethnic group may vary significantly from that seen in another ethnic group. While there are no substantial studies to provide statistics, it is widely believed that Caucasians have fewer HLA types compared with other ethnicities. Therefore, Caucasians are more likely to locate a donor match than patients from other ethnicities (eg, Asians, Indians, Hispanics, African Americans). This gap is further exacerbated due to a low number of donors among non-Caucasian ethnicities.

In the United States, the 2012 National Marrow Donor Program (NMDP) registry reported that 63% of adult donors were Caucasian, 27% were of a minority group, and 10% reported unknown race/ethnicity. The likelihood of finding a matched unrelated donor for a Caucasian is 93%, and a mere 66% to 82% among minorities, depending on the ethnicity. African Americans are the least likely to find a match.

According to the National Cord Blood Program, African Americans make up only 12% of the US population. There would have to be 3 times more African Americans than Caucasians in a bone marrow donor registry to have the same likelihood of finding a match.

	Other factors that limit transplants in minorities

Additionally, in India, where the current population is roughly 1.2 billion,

 only about 45,000 people have signed up as bone marrow donors.

 Comparative figures from the US NMDP indicate over 10 million donors. About 1 in 300 will be selected as a best possible donor.

In addition to the fact that minorities are at a disadvantage for stem cell transplants because there are fewer people to match with, other factors further limit the number of stem cell transplants in minority groups.

Religious beliefs, myths, and a lack of awareness often discourage people from donating.

Among the many prevailing myths, there is the myth that stem cell donation is a painful procedure accompanied by several side effects. In many countries, blood donation is considered painful and/or harmful.

 Based on my experience, patients do not like the idea of invasive needles being pushed into their bone for bone marrow. However, they are not aware that stem cells can also be donated by peripheral blood, just as in platelet donation.

Additionally, many cultures throughout the world do not emphasize the importance of public charity. Such acts of service are typically saved for family and friends.

	Cord blood transplants expand among minority groups

Although there are a limited number of stem cell transplants among minority groups, there has been an increase in the proportion of cord blood transplants. For example, the NMDP recently reported that 44% of transplants in minority groups were cord blood transplants.

 During a cord blood transplant procedure, a partial match is acceptable. However, cord blood transplants are more complicated, as the number of cells is much lower. A cord blood transplant also has a longer lead time for engraftment, which may result in an increased incidence of infections and complications.

To address the challenge of the limited availability of stem cell donors in non-Caucasians, it is vital that we increase awareness through more campaigns that are targeted specifically to minorities. These campaigns should be publicized in areas where specific minority groups dwell.

At an international level, the myths regarding stem cell transplantation need to be addressed by informing the general public that donations can be collected through peripheral blood, just as in platelet donation, and not through the bone. An increase in the absolute number of patients who register worldwide increases the chance of minority patients in the United States finding a match. Even 1 extra life saved can make these actions, although challenging, worthwhile.

			Malhotra A. Stanford professor dies as donor hunt fails. 

			Bone marrow transplantation and peripheral blood stem cell transplantation. Nation Cancer Institute website. http://www .cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant/print. Published August 12, 2013. Accessed January 2, 2014.

			Shiina T, Inoko H, Kulski JK. An update of the HLA genomic region, locus information and disease associations: 2004. 

			Setterholm M. Using HLA allele and haplotype associations: guess who. World Marrow Donor Association [presentation].

			National Marrow Donor Program. HCT presentation slides. Be The Match website. https://www.bethematchclinical.org/Resources-and-Education/HCT-Presentation-Slides. Accessed January 2, 2014.

			Why is cord blood important for ethnic minorities? National Cord Blood Program website. http://www.nationalcordblood program.org/qa/what_is_significance.html. Accessed January 2, 2014.

			India’s population 2013. IndiaOnlinePages.com website. http://www.indiaonlinepages.com/population/india-current-population.html. Accessed January 2, 2014.

			Datri brings together the donor and recipient of India’s first successful unrelated Blood Stem Cell transplant facilitated by an Indian Registry. ICTPost.com website. http://ictpost .com/health-directory/?p=775. Published November 26, 2013. Accessed January 2, 2014.

			National Marrow Donor Program. National Marrow Donor Program and Be The Match key messages, facts & figures. Be The Match website. http://bethematch.org/News/Facts_and_Figures_%28PDF%29/. Updated January 2013. Accessed January 2, 2014.

			Switzer GE, Bruce JG, Myaskovsky L, et al. Race and ethnicity in decisions about unrelated hematopoietic stem cell donation. 

			Office of Inspector General. National Marrow Donor Program progress in minority recruitment. Report OEI-01-95-00120. Published December 1996.

			Moretta A, Maccario R, Fagioli F, et al. Analysis of immune reconstitution in children undergoing cord blood transplantation. 

To address the challenge of the limited availability of stem cell donors in non-Caucasians, it is vital that we increase awareness through more campaigns that are targeted specifically to minorities. 

Prerna Mewawalla, MD

Articles

Dr Mewawalla on Unmet Needs After Early CAR T-Cell Therapy in Relapsed/Refractory Myeloma

Dr Mewawalla on the Real-World Roles of Cilta-Cel and Ide-Cel in R/R Myeloma

Smart Apps for Smart Docs

Limited Availability of Non-Caucasian Stem Cell Donors: A Growing Problem?