The American Society of Clinical Oncology (ASCO) projects significant shortages of practicing oncologists compared with patients with new cancer diagnoses and existing cancer by 2025.

 For an oncologist entering the workforce, this is valuable news. The job search for physicians in the COVID-19 and post–COVID-19 era will undoubtedly be different from any years before 2020. Nonetheless, fellows in hematology-oncology graduating in this time and recruiting in the next year will still have to go through requisite steps to secure desired jobs and positions. Through my own experiences this past year, I hope to highlight some key elements of the process, including unexpected pitfalls and pleasant surprises.

Growing up, I spent every vacation and many weekends in Maine, and even went to college in Brunswick, Maine. But, I didn’t learn about a nonprofit health care system called Maine Health until the 2019 ASCO Annual Meeting when I was a first-year fellow. Maine Health operates the state’s only academic medical division and is very closely affiliated with Tufts University, my residency alma mater.

I thought this would be a no-brainer in terms of personal and career fi t. I had my first job interview there in January of my second year of fellowship—nearly 18 months before graduation. The interview went well and both parties left feeling that we were close to being on the same page.

Summer came about and I went on my second, seemingly perfunctory, interview and thought that I had a job lined up. Ultimately, the job offered to me by Maine Health turned out not to be the one I thought I’d have. Instead, they had an opening for a community oncology job with academic affiliation in Brunswick.

The role and location of the practice did not match my expectations. It’s difficult to convey in print the disappointment that I felt at that time, knowing that I’d have to embark upon more interviews and that my dream of settling down in Maine as an academic oncologist would not yet come to fruition.

I uploaded my curriculum vitae to online physician job sites and within days I was fielding interview requests from health systems, hospitals, and practices around the country. I learned so much, so quickly about the job market only after opening myself up to various opportunities across the entire country. However, had this all happened later in the job search cycle, it would have been a painful lesson to not invest too heavily into your 1 potential dream job.

Consider Location and Employment Settings

As much as I love Maine, I knew I didn’t want to practice only in Brunswick. Location has a significant influence on the type of opportunities available to you and may affect the range of compensation you can expect. For example, New York City, Boston, and San Francisco are known for low physician salaries overall and hematology-oncology is no exception.

However, these cities offer copious opportunities for academic faculty positions because of their tight clustering of medical schools and cancer centers in a small geographical region. Similarly, these are some of the best cities for those considering a pivot to an industry job.

After several years as an academic oncologist, preferably with clinical trial experience, you will likely see high demand for your skill set from pharmaceutical companies, regulatory agencies, and clinical practices. A skill set that includes patient care and research experience allows for a transition to almost any oncology job out there, and major cities allow you to change jobs or industries while staying in the same area.

That said, there are advantages to working outside major population centers as well. There is great demand for well-trained oncologists to practice outside big cities in the United States. One in 6 Americans lives in a rural community and patients there have similar cancer incidence to those in urban centers.

I realized during my interview process that many communities with lower population density have impressively sophisticated medical communities where I could employ my skills and training. Contrary to most professions out there, physicians, including oncologists, are often financially rewarded for practicing in more remote locations. Many rural or suburban practices off er larger sign-on bonuses, loan repayment, and higher starting salaries than those in urban locations.

Finally, consider the implications of noncompete clauses in offers of employment when choosing where to work and live. In my experience, almost everything in a contract, including a noncompete clause, is negotiable, though sometimes unavoidable. However, if your contract includes a geographical noncompete clause and you work with the biggest player in a more remote community, you may be forced to move if things don’t work out.

Of course, there are benefits and drawbacks to the different types of oncology jobs (

). You’ll have to weigh financial considerations, potential for teaching or research, level of autonomy, influence over health policy, and overall population impact. During training, we have largely been exposed only to academic models of medicine, practiced within the confines of a hospital or health system, which does not encompass the full range of professional opportunities.

 Factors to Keep in Mind When Choosing an Oncology Job

Personally, I had eschewed ideas of joining a private practice and only somewhat considered moving to industry. However, during this job search process, I realized that I highly value my autonomy and independence, and typically do my best work when I am my own sole motivator.

I also wanted to maintain a strong presence in clinical trials. I found a compromise by joining a private practice with a strong clinical trials program, recognizing in advance that much of my research time will have to come out of my free time after a potentially busy clinic day.

Some of my co-fellows chose to pursue clinical educator or research physician academic tracks at various academic centers where they will have to climb the ivory tower and navigate health system politics while writing investigator-initiated studies and building their reputations.

Whether you join a practice as a partner track junior physician, join a pharmaceutical company as an associate medical director, or join an academic center as junior faculty, gratification is unlikely to be instant. It will require hard work, consistency, and perseverance. Tian Zhang, MD, an academic genitourinary specialist and clinical trialist at UT Southwestern Medical Center, says, “Delayed gratification is gratification enough.”

In the end, aside from the perks and annoyances of our jobs, we must be content with the work that we do day in and day out. I hope you will explore many opportunities to discover your ideal job, and I hope that you will find fulfill-ment with the job you ultimately choose.

Yang W, Williams JH, Hogan PF, et al. Projected supply of and demand for oncologists and radiation oncologists through 2025: an aging, better-insured population will result in shortage. J Oncol Prac. 2014;10(1):39-45. doi:10.1200/JOP.2013.001319

2020 Snapshot: State of the oncology workforce in America. JCO Oncology Practice. 2021;17(1):30. doi:10.1200/OP.20.00577

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The American Society of Clinical Oncology projects significant shortages of practicing oncologists compared with patients with new cancer diagnoses and existing cancer by 2025.

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Multiple myeloma is a plasma cell malignancy that accounts for approximately 1% of new cancer diagnoses per year. The development of a combination approach of mainstay therapies including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti–CD-38 antibodies has greatly improved up-front remission rates and response duration and prolonged overall survival in the past decade. However, for patients who have been heavily exposed to or are triple or penta-refractory to these classes of therapy, survival is under 1 year.

 Therefore, the emergence of cellular-based therapies represents a major opportunity to improve outcomes in the heavily pretreated and refractory myeloma population.

Chimeric antigen receptor (CAR) T-cell therapies approved by the FDA for several relapsed and refractory B-cell lymphomas are presently under investigation in a variety of treatment line settings for multiple myeloma. As more patients in the community become eligible for CAR T-cell therapies, community oncologists will need to be increasingly familiar about the various products, including their immediate and longer-term risks. In addition, it is key to understand the optimal time for referring these patients to an academic institution, as well as how to manage the requisite post CAR T-cell therapy in the community setting.

The State of Current BCMA-Directed CAR T-Cell Therapy

The major CAR T-cell therapies in trials for multiple myeloma are directed toward B-cell maturation antigen (BCMA), a surface antigen expressed on B cells starting from their period of development in the germinal centers onward and persisting through the time of plasma cell differentiation. BCMA is minimally expressed in normal human tissues but is heavily expressed on myeloma plasma cells. This allows for safe and intentional targeting of neoplastic myeloma cells using CAR T-cell technology.

The first FDA-approved commercial CAR T-cell therapy will likely arrive in the first quarter of 2021. Patients enrolled on the initial BCMA CAR T-cell trials were required to have had 3 or more prior lines of therapy with exposure to a PI, an IMiD, and an anti-CD38 monoclonal antibody.

The earliest trial was the KarMMa-1 study (NCT03361748) of idecabtagene vicleucel (ide-cel, previously bb2121), which demonstrated an overall response rate (ORR) of 73% and a median progression-free survival (PFS) of 8.8 months in all dose levels. Additionally, a median PFS of 12.1 months was observed in the highest dose level of CAR T cells (450 × 10

 Patients on this trial (n = 128) had a median of 6 prior lines of therapy, and 84% were triple refractory.

A concurrent trial, CARTITUDE-1 (NCT03548207), studying JNJ-4528 (ciltacabtagene autoleucel in China), also targeting BCMA, demonstrated an unprecedented 100% ORR in patients, with 86% achieving stringent complete response (sCR), the deepest response level by International Myeloma Working Group criteria.

 In the most recent evaluation of PFS, 86% of patients on CARTITUDE-1 had not progressed in disease at a median follow-up time of 9 months.

 New data for JNJ-4528 and the other CAR T-cell therapies being investigated will be made available during the 2020 American Society of Hematology Annual Meeting and Exposition in December and should further reinforce the potential for CAR T-cell therapy to deliver deep and durable responses to patients with multiple myeloma who are heavily pretreated.

What Type of Patients Might Benefit the Most From CAR T?

As in the case of BCMA, antigens for CAR T cells are chosen for their unique expression in tumor tissue and low expression in 

normal, healthy tissue. The complications that occur in patients receiving CAR T-cell therapy will be largely specific to the targeted antigen. Patients must undergo a multistep process to safely and effectively undergo CAR T-cell treatment and should know up front about the process involved.

The initial step involves leukapheresis, or collecting the patient’s T cells. Once this is completed, the patient must wait 3 to 5 weeks for typical manufacturing of their CAR T cells at a production facility. If required, patients typically can undergo bridging chemotherapy during this waiting period to maintain their disease, particularly if myeloma progression is accelerating. Once the patient’s CAR T cells are produced, the patient will undergo lymphodepletion (typically with fludarabine/cyclophosphamide) for 3 days before being infused with prepared CAR T cells. Patients must have sufficient health reserve to withstand the potential adverse effects (AEs) associated with CAR T-cell therapy, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Therefore, early referral to an academic center is key to getting these patients on therapy at the optimal time.

Immediate and Longer-Term Complications of CAR T-Cell Therapy

CRS is the most common acute AE that occurs in patients treated with CAR T-cell therapy. It occurred in nearly 9 out of 10 patients in the KarMMa-1 and CARTITUDE-1 trials, though severe CRS occurred only in 5% to 7% of patients.3,5 CRS is the phenotypic presentation of a supraphysiologic production of cytokines prompted by immune cell activation, including T cells, macrophages, and monocytes (

 ). Preclinical models have shown that macrophages amplify CRS severity and are the source of several of the culprit cytokines of CRS, including interleukin (IL) 6, IL-1, and IFN-γ. CRS onset occurs variably depending on the CAR construct used.

For example, CRS occurred at median 1 day after infusion of ide-cel, whereas CRS occurred at median 7 days after infusion of JNJ-4528. Our primary treatment for CRS is tocilizumab (Actemra), a monoclonal antibody directed against IL-6; its use does not diminish efficacy of CAR T cells. Subsequent agents such as the IL-1 receptor antagonist anakinra (Kineret), anti–IL-5 monoclonal antibody siltuximab (Sylvant), and corticosteroids may be employed for severe cases of CRS.

The second notable AE associated with CAR T-cell therapy is ICANS, which is defined by the American Society for Transplantation and Cellular Therapy as “a disorder characterized by a pathological process involving the central nervous system….Symptoms or signs can be progressive and may include aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral edema.”

 A primarily encephalopathic picture appears when patients develop ICANS, which typically occurrs later than CRS. The primary treatment for ICANS involves corticosteroids such as dexamethasone, initially every 6 hours with a quick taper as symptoms start resolving.

Signs and symptoms of neurotoxicity should be screened at least daily during the acute CAR T-cell treatment period and can be assessed with validated tools such as those from CAR T-cell therapy-associated TOXicity (CARTOX) Working Group or the Immune-Effector Cell-Associated Encephalopathy (ICE) tool.6 Severe neurotoxicity occurred at only a 3% rate in KarMMa-1 and CARTITUDE-1 and can be treated readily if caught early with close monitoring.

Other common AEs such as cytopenia and infection may occur during and after the period of CAR T-cell infusion and expansion. Anemia, thrombocytopenia, or neutropenia may occur for months after the initial treatment 

period, and clinicians should utilize supportive transfusions and/or granulocyte colonystimulating factor and thrombopoietin mimetics as indicated.

Cytomegalovirus quantitative polymerase chain reaction should be checked monthly. If the patient is persistently neutropenic, opportunistic infections should be considered. Intravenous immunoglobulin should be administered before initial lymphodepletion, but also every month for 6 months after CAR T-cell infusion and during winter months if the patient has a history of recurrent infections. In addition, patients should be vaccinated at 1-year post CAR T-cell therapy; a recommended vaccine schedule is included in 

Table 2. Recommended Vaccine Schedules After CAR T-Cell Therapy

The multiple myeloma treatment landscape is rapidly evolving, with many exciting new therapies on the forefront for relapsed and refractory multiple myeloma. CAR T-cell therapy is a 1-time treatment that allows patients to achieve deep and durable remissions without the need for the usual continuous cancer-directed treatments. The aforementioned trials and therapies have paved the way for subsequent iterations of cellular therapies. These include non–BCMA-targeted CAR T cells; next-generation CAR T cells with improved costimulatory domains for improved safety, efficacy, or faster production; and allogeneic CAR T cells derived from pluripotent stem cells available off the shelf to patients. In the coming year, as commercially available myeloma CAR T-cell therapies are approved, it will be even more important for community oncologists to better understand these therapies so they can offer them to their patients.

Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. 

. 2019;33(9):2266-2275. doi:10.1038/s41375-019-0435-7

Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. 

. 2019;380(18):1726-1737. doi:10.1056/NEJMoa1817226

Munshi NC, Anderson LD, Shah N, et al; KarMMa Study Investigators. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): initial KarMMa results. 

. 2020;38(suppl 15):8503. doi:10.1200/JCO.2020.38.15_suppl.8503

Madduri D, Usmani SZ, Jagannath S, et al. Results from CARTITUDE-1: a phase 1b/2 Study of JNJ-4528, a CAR-T cell therapy directed against B-cell maturation antigen (BCMA), in patients with relapsed and/or refractory multiple myeloma (R/R MM). 

. 2019;134(suppl 1):577. doi:10.1182/blood-2019-121731

Berdeja JG, Madduri D, Usmani SZ, et al. Update of CARTITUDE-1: a phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma. 

. 2020;38(suppl 15):8505. doi:10.1200/JCO.2020.38.15_suppl.8505

Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. 

. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758

The emergence of cellular-based therapies represents a major opportunity to improve outcomes in the heavily pretreated and refractory myeloma population. 

Bo Wang, MD

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CAR T-Cell Therapy for Multiple Myeloma: What Community Oncologists Need to Know