Sairah Ahmed, MD, associate professor, director of the CAR T Program, and inpatient medical director, Department of Lymphoma/Myeloma and Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses optimizing treatment with axicabtagene ciloleucel (axi-cel; Yescarta) in large B-cell lymphoma (LBCL). 

Currently, clinical trials are evaluating methods to utilize axi-cel earlier for patients with LBCL, as well as how to minimize the toxicity and improve efficacy associated with the CAR T-cell therapy, says Ahmed. Findings from an analysis, which were presented during the 

2021 Transplantation & Cellular Therapy Meetings

, demonstrated that patients with LBCL who did not derive a complete response to any line of prior therapy predicted for inferior outcomes with axi-cel.

As such, these data suggest that more aggressive therapeutic intervention should be utilized prior to or after CAR T-cell therapy administration in certain patient populations, Ahmed explains. Although CAR T-cell therapy remains a relatively new modality to manage LBCL, it is important that the field develops a greater understanding of how to tailor treatment to individual patient populations, concludes Ahmed. 

Videos

Sairah Ahmed, MD, discusses optimizing treatment with axicabtagene ciloleucel in large B-cell lymphoma.  



Dr. Ahmed on Optimizing Treatment With Axi-Cel in LBCL 

Sairah Ahmed, MD, associate professor in the Department of Lymphoma/Myeloma and Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the efficacy of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with refractory large B-cell lymphoma (LBCL) who achieved complete remission (CR) to any prior treatment versus those who were primary refractory.

Findings from a single-center retrospective review, which were presented at the 2021 Transplantation and Cellular Therapy Meetings, demonstrated that the CR rate with axi-cel was significantly lower in patients who were primary refractory compared with patients who had achieved a CR to prior therapy, at 47% and 72%, respectively (

The median progression-free survival was 5 months in the primary refractory group versus 26 months in the group that had attained a prior CR (

 = .10). The median overall survival was not reached in either group, although it was shorter in patients with primary refractory disease. Despite the numerical difference, this parameter was not found to be statistically significant, says Ahmed. These findings suggest that the CR denotes a difference in overall outcomes with CAR T-cell therapy, concludes Ahmed.

Sairah Ahmed, MD, discusses the efficacy of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with refractory large B-cell lymphoma (LBCL) who achieved complete remission (CR) to any prior treatment versus those who were primary refractory.

Dr. Ahmed on Axi-Cel Benefit in Patients With Primary Refractory LBCL

	For an incoming first-year hematology/oncology fellow, July 1st is when you are once again the new kid on the block. Whether you are starting a fellowship at your home institution or in a new city, July 1st marks the beginning of the final phase of training that we have worked so hard to arrive at. Although completing fellowship at your home institution may give you a leg up on finding the bathroom, it will not, unfortunately, lessen the learning curve inherent to the most challenging year of training. And although you may initially still perceive yourself as a third-year resident mastering the skills of hypertension and diabetes management, to your patients, you are now their oncologist.

	The field of hematology/oncology is unlike many other medical sub-specialties in that there is very little exposure to it during residency. During the earlier part of your first year, you will rattle-off chemotherapy side effects and tell patients and their families “what they can expect.” At that point, however, you may barely be able to pronounce the drug, let alone provide patients the knowledge they need to prepare for toxicities. I spent my first year of fellowship studying the “hallmark” articles and memorizing National Comprehensive Cancer Network (NCCN) guidelines. I imagined myself going home after work to sit and read about each of my clinic patients. As the demands of first-year fellowship became obvious, however, I realized that this was not how I was going to gain my knowledge. Between learning to write orders, performing bone marrow biopsies, and running the oncology services, there were many days when I was glad to have an opportunity to eat lunch, let alone absorb the latest 

	Most of the knowledge I attained during the first year of fellowship came from interacting with patients and learning how to take care of them. As you make your way through the first year, you’ll realize that you are no longer memorizing a list of side effects, but rather explaining to your patients the toxicities that you have actually witnessed. As the initial feelings of being overwhelmed wear off, you will slowly become comfortable with this “new language” of oncology.

	As I entered fellowship, I prepared myself for the academic challenge and even cleared my weekends in anticipation of spending most of my time at the hospital. I studied NCCN guidelines and tried to read everything that I thought would prepare me. It was the emotional toll of learning how to be an oncologist, however, that proved to be the most challenging. No matter how hard I searched, I could not find an algorithm that explained how to tell my 21-year-old patient and his family that his cancer had progressed and he was dying. This part of the job did not become easier for me emotionally during the first year. As I learned the natural history of diseases, however, I became more comfortable with these difficult conversations.

	What surprised me about these encounters was the fulfillment and great satisfaction I found in supporting my patients through their treatment journey, whether it meant receiving more chemotherapy or making the difficult decision to transition to hospice. I was fascinated by the fact that cancer is the ultimate equalizer—it disregards race, gender, and socioeconomic status, and gives patients the same hopes and fears. As the year progressed, I grew to appreciate that fact that although the victory of remission is obvious, the less obvious victories such as controlling pain or nausea truly impact our patients’ quality of life.

	The first year of fellowship was more challenging for me than any other time during my training. At this point in our lives, many of us have families and other obligations that may seem incompatible with being a first-year fellow. After finishing clinic most days, I would frantically run to to pick up my two-year-old daughter from daycare by 6:00 pm. While balancing family and fellowship is not easy, it is possible to juggle both with careful planning, support from your family, and prioritization. In my experience, a personal support system—from a spouse, family member, friend, or coworker&mdash;is crucial during the first year of fellowship. Caring for patients with cancer requires you to give yourself both academically and emotionally, and having a support system is very important as you learn how to handle the death and dying of your patients.

	Another key to surviving your first year of fellowship is relying on the second- and third-year fellows for help as you navigate the first few months. Although senior fellows may seem like they have everything figured out as they diligently work on research projects and quote data from hallmark articles, remember that they started out just like you. The worst mistake you can make is not asking for help when needed. The senior fellows and attendings would rather be asked the important questions than have serious mistakes made.

	As you settle into your first year, you will become comfortable performing bone marrow biopsies and will not be scared every time your pager goes off. You will inevitably become more comfortable with the never-ending thrombocytopenia consults and will start thinking about your future as an oncologist. Finding a meaningful mentor that understands your clinical and research goals will be important to establish early. Many times, these relationships happen naturally as you get to know the faculty and learn about their interests. On the other hand, you may find yourself intrigued with a certain research topic and need to seek out people in the department. Either way, a good mentor will help develop your interests and open up opportunities.

	It is now July 1st of my second year, and although I can fully recognize how much I have learned about the science of oncology and the art of treating patients, I still cannot pronounce all of the chemotherapeutics and need to look up the staging systems of some malignancies. After so many years of learning general medicine, you have finally arrived at your specialty of choice. As you battle your way up the learning curve, it may feel at times that you are simply trying to survive. Rest assured that you will approach July 1st a resident, but leave your first year of fellowship as an oncologist.

Sheetal Kircher, MD, completed her first year of fellowship at Northwestern Memorial Hospital in June 2010.

	During my first year of fellowship in a combined hematology and oncology program, I spent much of the year trying to balance my clinical obligations with my life outside of the hospital. My first year involved 11 months of inpatient ward training in malignant hematology, solid oncology, and stem cell transplant rotations, interspersed with inpatient consult in benign hematology and oncology. In addition to the rigorous inpatient schedule, I also spent three half-days in disease-specific outpatient clinics. While the learning curve was steep, the bigger challenge was balancing work demands with a husband and toddler at home. I anticipated that the second year of fellowship would be the time to catch my breath, and in many ways, this was true.

	Although I felt an incredible sense of relief after the clinical marathon of first-year fellowship, my second year has been busy in a different way, with a shift in focus toward pursuing clinical, translational, or basic science research. The daily schedule during my second year provided me with a mental and physical breather. Holding a pager six days per week during the first year created a mental “bond” to the hospital; even when I was physically away from the hospital, it was hard to truly “exhale” and reflect. During my second year, I finally felt that I could exhale. Upon reflection, it became clear that although the first year of fellowship was intense, I had gained an immeasurable amount of knowledge in a short time. I also gained a sense of confidence and pride knowing the myriad challenges I overcame. As a second-year fellow, I was able to counsel the incoming first-year fellows and reassure them that the first year would not only be survivable, but also an incredible chance to lay a strong foundation for their career. Perhaps one of the biggest distinctions between the first and second year is that the second year was a time to solidify my clinical knowledge, build my resume, and prepare for the process of applying for jobs, which will begin relatively early during the third year.

	Much of the second and third years of fellowship are designed to allow time for research pursuits, particularly for physicians who are interested in an academic career. For those who hope to pursue a career in academic medicine, most agree that a successful and productive second year of fellowship begins with identifying the right mentor. Ideally, mentorship should begin during the first year of fellowship, although expectations for research productivity should be modest. If nothing else, establishing a mentor or network of mentors during the first year and meeting on a regular basis can help create the framework for a productive relationship and enable you to “hit the ground running” at the beginning of your second year. This is especially true for those who begin fellowship with a particular disease focus or interest, or who develop one early on. An ideal mentor is someone whom you respect; who is experienced and academically successful; and who is approachable, available, and invested in your own success.

	Many mentors may have projects that are near completion or in various stages of development, and a fellow is the ideal candidate to complete them. Faculty are usually very receptive to fellows who are interested in helping complete projects. This can be an opportunity for fellows to gain skills that will be applicable in the future, even if their disease focus or interests change with time. Such a situation is a “win-win” for both parties—the mentor benefits from the outside help, while completed projects can help fellows “build” their resumes and provide them with an opportunity to present at conferences and meetings. Although projects that are initiated during fellowship often take years to complete and may continue beyond fellowship, they can provide fellows with valuable skills that can transcend their professional career.

	For fellows interested in pursing a career in academic oncology, the second year of fellowship is an important time to consider applying to programs such as the American Society of Clinical Oncology (ASCO)/American Association for Cancer Research or the American Society of Hematology (ASH) Clinical Research Training Institute workshops to gain further skills useful in clinical research. These workshops focus on teaching fellows and junior faculty the various methods of clinical trial design and technical writing, and tend to take place in July and August, with application deadlines as early as December. If you are interested in applying for these programs, it is helpful to know about them ahead of time in order to identify a project for the application process. Furthermore, the second year of fellowship is a time to consider applying for fellow training grants that are available through various organizations, such as the ASCO Young Investigator Award or the ASH Fellows training awards. This is also an ideal time to begin projects that could be used when you apply for these awards during the third year of fellowship.

	The second year provides plenty of time to broaden your knowledge and solidify everything learned during the first year. Most fellowship programs have numerous conferences and tumor boards that can be more consistently attended during the second and third years. During your first year of fellowship, it can be a challenge to attend all of the didactic opportunities that are available while simultaneously balancing your clinical responsibilities. The second year may also provide more time to read the primary data in order to support your clinical decisions. Most fellowship programs have physicians continue in one or more clinics during the second year of fellowship while scheduling less inpatient service. This is crucial for developing and strengthening the clinical skills necessary for going into practice after fellowship, especially for those who may be interested in clinical practice.

	Whether you are pursuing an academic or clinical position post-fellowship, being productive during your second year is important. The time to start applying for jobs comes sooner than imagined (or at least sooner than I had imagined). Most faculty advised me that for academic jobs, resumes are sent as early as July through October. Since the job search begins early in the third year of fellowship, the latter part of my second year was also dedicated to updating my resume, completing projects that could be included in my resume, and asking for letters of recommendation and references. I personally chose to start the process quite early because I knew that I would be on maternity leave when I would need to send resumes to various institutions. If you know very early which particular institutions or geographic locations you prefer, the annual ASCO meeting is a good venue to begin to make some contacts for the job search.

	While the first year of an oncology fellowship may be the most physically and emotionally demanding, the second year is crucial for training and preparing physicians for their career post-fellowship. For me, the second year of fellowship was a time to really get involved with clinical research to prepare me for an academic career and improve my skills as a clinician.

Josephine Feliciano, MD, completed her second year of fellowship at Northwestern University Feinberg School of Medicine in June 2010.

	Congratulations—you’re a third-year fellow and there’s finally a light at the end of a long, dark tunnel. Suddenly “the real world” is a tangible reality. After years of training, you are entirely capable of dealing with the science of medicine, from looking up NCCN guidelines to treating solid and hematologic malignancies, from writing review articles to talking to patients about goals of care. An acute leukemia at 3:00 am no longer strikes fear in your heart. But nothing in training has prepared us for the next steps&mdash;looking for a job, navigating contracts, and trying to decide where you will be happiest for the rest of your professional career. Scary thought, huh?

	One of the first decisions to be made is whether to pursue a career in academia or private practice. While some decided this long ago, the choice isn’t so black and white for the rest of us. So why choose private practice over academia? The obvious answer is monetary compensation, but ultimately, it’s about personality. Being part of a practice provides a great deal of control over where, when, and for whom you work. You are the master of your fate and captain of your soul—how many times has that happened before? After years of self-discipline, finally what you want matters; how much it matters may be up for debate!

	On the other hand, why choose academia over private practice? Teaching, clinical and translational research, and subspecializing in a specific malignancy are all included in the mix, but again, it’s personality. Those who choose academia like to be constantly challenged and crave the feeling of juggling several balls at the same time. They focus on multiple problems while trying to advance scientific knowledge, always hoping that one of those balls won’t go splat at the wrong moment!

	Below is my advice for navigating the details after the private practice vs academia decision is made.

 Once the geographic area is decided, start networking with friends, colleagues, and physicians in the area—both in other specialties and your own. Determine which practices you’re interested in, whether they’re hiring, and send out interest letters and your curriculum vitae (CV). An extremely important asset are your faculty; the connections they have within the community and across the country is an invaluable tool&mdash;USE THEM!

	By September, actively gather information about where to apply, and by November, send out CVs and set up interviews. Winter and spring will be an interview merry-go-round. Ask the questions you never asked in residency or fellowship interviews: What is the base salary? Are there bonuses? How does partnership work? How is vacation decided? What is the call schedule? What are the details of the non-competence clause? The list is endless and will reflect what is most important to you. Remember to trust your instincts and pay attention to the intangibles—all the things that make you love your work environment. Don’t underestimate the importance of these factors.

	Before accepting the final offer, make sure a lawyer reviews the contract. The devil is in the details, and your responsibilities should be clear prior to signing on the dotted line.

 Geographic location, a specific research interest, or treating a particular tumor type may drive your choice. Sometimes having more than one goal makes it harder to find a perfect fit. Again, talk to faculty, as they will have the inside track on open positions or cancer centers that are hiring. Former fellows and colleagues are great resources to tap as well. Use ASH and ASCO to network; it may lead to interviews later.

	In September, start sending out letters of intent with CVs attached. Don’t limit the search to institutions with open positions—include all institutions you’re interested in. Sometimes the job you want isn’t being offered yet, but it never hurts to ask. Gently having faculty mentors call or email can also help open the door to an interview.

	Academic interviews usually include a job talk, which may entail discussing the clinical research you’re involved in or detailing the time spent in a basic or translational lab. THE most important aspect of the talk is your grasp of the subject matter. From the mundane to the most technical, you want to impart to the audience how intimately involved in the project you were, not that the post-docs in your lab did most of the work and you can’t tell the difference between a Western blot and a microarray. If you’re discussing a clinical project, know how the information was collected and how to interpret the statistics, and be able to explain the hypothesis behind the study. No one expects entirely independent data; however, if you can’t intelligently discuss your project, it’s very hard to be taken seriously. Confidence and the ability to answer queries serenely will make you stand out from the rest of the crowd.

	The tricky part is making sure the job they offer is the one you want. Is there enough research time? How does the tenure track work? How many clinics during the week? How many service months? How is salary determined (RVUs vs grants)? And finally, if your heart is set on lung cancer but the open position is in lymphoma, are you willing to compromise? Once more, get a lawyer to review the contract, although most institutions have basic stipulations that are set in stone.

	Last but not least, if you’re slightly insane, follow me down the path to yet another fellowship. There are a few options if you haven’t tired of a training salary and want to attain PGY-8 status. I chose a stem cell transplant fellowship, but there are others in transfusion medicine or pharmacogenomics. The application process was circumspect compared to a job hunt or even prior training positions. There are a very finite number of institutions that offer these positions and interviews are the same flavor as before, just longer.

	In the words of George Burns, “I look to the future because that’s where I’m going to spend the rest of my life.” After the stress and confusion wear off, you’ll realize that the hardest part is over and now begins the start of your career!

	A few words of wisdom for incoming first-year fellows:

	• This is toughest year of training you’ll ever experience. You will learn an immense amount, but there will be days (lots and lots of days) that you want to give up. Don’t! It will get better and you will sleep again.

	• Ask questions. You’re in fellowship to learn; the aim is for you to be taught and trained well.

	• Remember internship and the mantra “Eat when you can, sleep when you can, and just get through today.” Relearn the mantra.

	• It’s hard to tell people they are dying and you can’t change that reality. Burnout is real and you have to avoid it. Use everything you can to keep centered— family, friends, co-fellows, sports, alcohol…ok, I was kidding about the alcohol! But expect the emotional roller coaster; we all get on the ride but aren’t ready for the sudden fall.

	Understand that difficult patients (and families) are often a manifestation of fear and loss of control. It’s seldom personal and they don’t really hate you. Avoid saying, “I understand what you’re going through” unless you’ve experienced the same. Try, “I can’t imagine what you’re going through,” and then just listen….a lot.

Sairah Ahmed, MD, completed her third year of fellowship at Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, in June 2010. She is starting a stem cell transplant fellowship at MD Anderson Cancer Center in July 2011.

Articles

For an incoming first-year hematology/oncology fellow, July 1st is when you are once again the new kid on the block.

Sairah Ahmed, MD

Articles

Dr. Ahmed on Optimizing Treatment With Axi-Cel in LBCL

Dr. Ahmed on Axi-Cel Benefit in Patients With Primary Refractory LBCL

A Year-by-Year Look at a Fellowship Program