The Community Oncology Alliance (COA) has weighed in on a new system of higher value performance for oncologists announced by the Centers for Medicare & Medicaid Services (CMS), saying it is a step in the right direction but needs to be supported by broader reforms.

CMS on Thursday announced the launch of an Oncology Care Model (OCM) that contains goals and financial incentives for practitioners in cancer care. ASCO called it a landmark in making value-based oncology care an explicit goal; the COA agreed, but added, “It is critical that payment reform … must also be concurrent with an immediate fix to Medicare drug payments or all this payment reform will be for naught.”

“The model proposed by CMMI [Center for Medicare & Medicaid Innovation] is generally consistent with COA’s Oncology Medical Home payment model, although there are some questions and concerns that we need to address with CMMI, which has been very open to input,” the COA said in a statement.

The OCM represents the second in a series of specialty care models of Medicare payment, following the start last year of the Comprehensive ESRD Care Model for enhanced care to beneficiaries with end stage renal disease. OCM is a 5-year program set to start in 2016.

Participating providers will have to provide patient access around the clock, 7 days a week to a clinician who has ready access to patient records. The OCM includes monthly, $160-per-patient care management payments along with performance-based payments for OCM episodes. The monthly payment is designed to support the cost of managing and coordinating care for Medicare patients.

The COA said in its statement that small practices are disappearing and need stronger support from CMS.

“For too long we have been fighting the detrimental consolidation of physician-directed cancer clinics into large hospital systems, causing chemotherapy and other cancer treatments to be more expensive for patients and payers, including Medicare,” the group said.

“Community oncology practices have been on the forefront of implementing novel payment reform pilots with private payers. It’s good now to see progress on the Medicare front.”

The OCM initiative is part of the Department of Health and Human Services’ “better, smarter, healthier” program to obtain more value for the healthcare dollars being spent through the Medicare program.

HHS hopes to link 30% of traditional or fee-for-service payments through Medicare to value-based care through alternative payment models, such as Accountable Care Organizations (ACOs) by the end of 2016 and 50% of payments to such models by the end of 2018.

“HHS is focused on three key areas: linking payment to quality of care; improving and innovating in care delivery; and sharing information more broadly to providers, consumers and others to support better decisions while maintaining privacy,” the release said.

The OCM will cover nearly all cancer types and is a multi-payer model that includes Medicare fee-for-service (OCM-FFS) and other payers such as commercial insurance plans or state Medicaid agencies. 

Articles

The COA has weighed in on a new system of higher value performance for oncologists, saying it is a step in the right direction but needs to be supported by broader reforms.

COA Says New Care Model Doesn't Go Far Enough

The American Board of Internal Medicine (ABIM) is making substantial changes to its Maintenance of Certification Program (MOC) for internists and subspecialists following strong objections to an MOC revision made last year designed to ensure doctors were at the top of their game.

“This change generated legitimate criticism among internists and medical specialty societies,” ABIM President and CEO Richard J. Baron, MD, said in an open email to the internal medicine community. “Some believe ABIM has turned a deaf ear to practicing physicians and has not adequately developed a relevant, meaningful program for them as they strive to keep up to date in their fields.”

The ABIM, whose changes a year ago made continuous assessment a feature of the MOC rather than once-in-10-years requalification, said it would immediately suspend MOC requirements for “practice assessment,” “patient voice,” and “patient safety” for at least 2 years.

“This means that no internist will have his or her certification status changed for not having completed activities in these areas for at least the next two years,” the email said.

The ABIM said those holding diplomas who are currently not certified but who have satisfied all requirements for MOC except for practice assessment will be issued new certificates this year.

Another change promised is to refer to diplomates’ MOC status as “participating in MOC” rather than “meeting MOC requirements.” This becomes effective within 6 months.

In addition, ABIM will update the internal medicine MOC exam to make it “more reflective of what physicians in practice are doing.” Those changes will be implemented in the fall of this year, with similar exam changes for subspecialties to follow.

MOC enrollment fees will remain at or below 2014 levels through at least 2017, the email said.

The ABIM also promised to develop new ways that internists could demonstrate medical knowledge by recognizing most forms of training approved by the Accreditation Council for Continuing Medical Education (ACCME).

The announced changes drew praise from the American Society of Hematology (ASH), which described them—particularly the suspension of the Practice Assessment requirement and the freeze on MOC enrollment fees¬–as “needed” and “a critical first step.”

The changes “follow years of criticism from ASH and mounting concerns voiced by ASH and other medical societies on the MOC requirements launched in 2014,” the ASH statement said.

The group, which is the largest professional society of hematologists, called for additional changes by ABIM to move the MOC away from “a closed-book examination delivered in a secure location to an examination experience that reflects current access to medical information.”

ABIM was founded nearly 80 years ago to create uniform standards for internists.

The practice assessment option for earning points toward MOC enables physicians to qualify based on participation in activities that improve the quality of patient care in their own practices. Physicians must implement changes and measure the impact of them.

The patient voice option for earning MOC points measures physicians on how well they incorporate the values and preferences of patients and their families when medical decisions are made. Completing patient surveys is one form patient voice measurement may take.

For patient safety, physicians may earn MOC credits by demonstrating foundational knowledge of current safety standards in the practice of medicine, prevention of adverse events and teamwork and care coordination.

While issuing an apology for the disruption it had caused with last year’s change, the ABIM stuck to its belief that more frequent MOC requirements would be beneficial. “While ABIM’s board believes that a more continuous certification helps all of us keep up with the rapidly changing nature of modern medical practice, it is clear that parts of the new program are not meeting the needs of physicians,” Baron said in the statement.

The ABIM promised to involve physician communities in planning for revisions to the MOC requirements. “The goal is to co-create an MOC program that reflects the medical communities’ shared values about the practice of medicine today and provides a professionally created and publicly recognizable framework for keeping up in our discipline,” the statement said. 

The American Board of Internal Medicine (ABIM) is making substantial changes to its Maintenance of Certification Program (MOC) for internists and subspecialists.

ABIM Rolls Back MOC Changes

When Marcela V. Maus, MD, PhD, thinks of the challenge of bringing chimeric antigen receptor (CAR) therapies to market in the battle against cancer, she is reminded of the auto industry’s first days.

American industrialists managed to streamline the process of making autos from one at a time to several rolling off the assembly line every minute, and the same kind of revolution could make CARs available on a broad scale, said Maus.

“Right now we’re at the very beginning, and I think this has tremendous potential to become something that can be manufactured by different groups in different plants all over the world,” Maus, director of Translational Medicine and Early Clinical Development at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia (UPenn), said in an interview.

The CAR technologies currently in development for hematologic cancers are a form of adoptive cell therapy in which the patient’s T cells are cultured and then primed to specifically recognize CD19, a protein expressed on normal and malignant cells of B-cell lineage. Thus, CD19 presents a suitable tumor-associated antigen against which to target anticancer agents (

The experimental technology has been successfully used to combat acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma, bringing many patients who participated in clinical trials into complete remission (

). The success of these therapies has caused much excitement, and hopes are high that the CAR approach could one day become a frontline treatment for many types of cancer, including solid tumors such as breast, ovarian, and prostate cancers.

Getting CAR therapies to market will involve the crossing of many hurdles, according to researchers, pharmaceutical executives, and industry observers, particularly in light of the manufacturing complexity and safety concerns involved. The drug industry, however, is more than willing to tackle the task of translating CAR therapies to clinical practice.

		Figure. Chimeric antigen receptor (CAR) technology

		Illustration courtesy of Novartis Pharmaceuticals

“It’s not without challenges,” said Usman Azam, MD, global head of the Cell and Gene Therapies Unit at Novartis Pharmaceuticals, which is working with UPenn to bring the CAR therapy CTL019 through clinical trials. “This is new for the agencies, it’s new for the hospital systems, it’s new for Novartis, but I think we have the building blocks in place. We have incredibly compelling data, and we’re going to be sharing some insights and a lot more at the upcoming ASH [American Society of Hematology] meeting. The data are showing great outcomes out to three years in the ALL population.”

Azam said his company is “doubling down” on immunotherapy, including CTL019, for which the FDA has granted breakthrough therapy status, allowing Novartis steady guidance throughout the clinical trials process to aid in bringing what could be a critical new agent to market as rapidly as possible.

Trials of CAR therapies by different industry/ academic partnerships have been conducted among pediatric and adult patients with relapsed or refractory leukemia, often resulting in complete remission lasting upward of a year or longer. The success for patients whose cancers were resistant to multiple other treatments has spurred huge investment to bring this technology out of the laboratory and into commercialization, and to explore the breadth of ways in which this form of immunotherapy could be employed.

Hoping to be the first to bring CAR therapy to market, Novartis in 2012 purchased the 173,100-sq-ft Morris Plains, New Jersey, plant that Dendreon had hoped would help make a financial success of sipuleucel-T (Provenge). The prostate cancer vaccine is similar to Novartis’ CTL019 in that both involve the removal of a patient’s T cells for modification at a manufacturing facility. In the $43 million acquisition, Novartis retained about 100 former Dendreon employees.

“That’s given us a very strong footing, both in terms of not just the facility but the talent and capability of those individuals,” said Azam. “That’s the unique edge that Novartis has. We’ve doubled down in this space by going big and bold. This is where our competitors are going to be struggling—actually getting the manufacturing knowhow. I do think we have the capabilities to get a leap start in front of the others.” But the race to market is not over yet, said Renier J. Brentjens, MD, PhD, a medical oncologist specializing in acute and chronic leukemias at Memorial Sloan Kettering Cancer Center in New York and a founding member of Juno Therapeutics, which over the past year has raised more than $300 million in startup capital to develop immunotherapies including T cells programmed to go after the CD19 antigen.

“Our early work in CD19 technology was instrumental in translating this medicine to the clinic and as such we were the first to publish significant clinical responses in relapsed B-cell ALL using these CAR T cells,” said Brentjens.

His group has been conducting research into CARs for more than a decade and reported on the first patients with ALL or CLL treated with the 19- 28z CAR therapy in 2011.

Brentjens and Azam anticipate that CAR therapy will be commercialized very soon. “I wouldn’t be surprised if by 2016 these CAR T cells are on the market,” Brentjens said. “There are now several companies that are developing this technology.”

MSK and Juno are working in conjunction with the Fred Hutchinson Cancer Research Center and the Seattle Children’s Research Institute, an example of the diversity of collaboration that has arisen.

Separately, Celgene and bluebird bio are working their own partnership on CAR therapy with Baylor College of Medicine, The National Cancer Institute is working with Kite Pharma, and MD Anderson Cancer Center is working with Johnson & Johnson. The biopharmaceutical company Cellectis has partnered with Pfizer and the French company Servier.

One key issue for investment partners and others endeavoring to bring this technology out of the laboratory is where in the spectrum of cancer-fighting agents CAR therapy will fit.

Some say the jury is still out on whether modified T cells will remain a treatment of last resort, owing to safety concerns and the availability of effective chemotherapy drugs that cost less. Cytokine release syndrome (CRS), the immune system’s feverish response to retargeted T cells, is interpreted by oncologists as a sign that CAR therapy is working, but it can also greatly sicken patients and even be fatal.

Daniel W. Lee, MD, of the Pediatric Oncology Branch of the National Cancer Institute, has been working with other oncologists to understand CRS better so that it can be managed successfully with the least amount of discomfort or danger to the patient. He believes that the problems with CRS can be overcome.

“We laid out a new proposed grading system for CRS because the old system just didn’t apply. And we also used that grading system to develop a treatment algorithm for when you should intervene in CRS to prevent grade 4 (life-threatening) toxicity,” Lee said. The system defines levels of toxicity and explains how to manage CRS.

“But the bigger issue is, can you even prevent it in the first place?” Lee asked. “To some degree you can. In our clinical trial, the patients with lower disease burdens have significantly lower risk of severe side effects. This gives us a clue as how to best incorporate this therapy in newly diagnosed patients.”

With a lower risk of exacerbating a patient’s condition, CAR therapy could prove very useful as frontline medicine, Lee said.

“If you can generate CAR T cells and reinfuse them in patients with newly diagnosed ALL at a time of minimal residual disease, they might have a low grade fever for a day or two, and that’s it. And that’s exceedingly nontoxic and may be the role for CAR T cells in the future,” said Lee.

		Table. Key Findings in Recent CAR Research Reports

							67% achieved 6-month event-free survival

							Durable remissions up to 24 months observed

					University of Pennsylvania/ Novartis

					Maude SL et al. N Engl J Med. 2014;371(16):1507-1517.

					15 patients with indolent B-cell malignancies and DLBCLs

							92% objective response rate in 13 evaluable patients, including 8 CRs, 4 PRs, 1 SD

							4 of 7 evaluable patients with chemotherapyrefractory DLBCL achieved CR

					Kochenderfer JN et al. J Clin Oncol. Published online August 25, 2014. doi:10.1200/JCO.2014.56.2025.

					21 pediatric and young adult patients with relapsed/ refractory B-ALL or NHL

							70% CR rate among 20 patients with B-ALL

							60% of patients with B-ALL achieved MRD Neg status

							10 patients with MRD Neg status subsequently underwent HSCT; all 10 disease free after 10 months’ median follow-up

					Lee DW et al. Lancet. Published online October 13, 2014. doi:10.1016/S0140- 6736(14)61403-3

					16 adults with relapsed/ refractory B-cell ALL

							7 patients successfully underwent allogenic HSCT after CAR therapy

							Defines diagnostic criteria for severe CSR

							Identifies serum C-reactive protein as indicator for CRS severity

					Davila ML et al. Sci Transl Med. 2014;6(224):224ra25.

		ALL indicates acute lymphoblastic leukemia; B-ALL, B-precursor acute lymphoblastic leukemia; CR, complete remission; CRS, cytokine release syndrome; DLBCL, diffuse large B-cell lymphoma; HSCT, hematopoietic stem-cell transplantation; MRD Neg, no minimal residual disease; NHL, non-Hodgkin lymphoma; SD, stable disease.

Lee and his colleagues have been testing CAR therapy on relapsed and refractory ALL pediatric patients, with positive results. “Our feasibility rate is 90%, and that’s from all comers,” he said, noting that patients were not prescreened to determine whether their T cells would multiply successfully once modified with the CD19 receptor, as was done by other groups.

Risks aside, there is also the issue of paying for the medicine, which could turn out to be prohibitively expensive, said Joseph Hedden, PhD, a pharma industry analyst with Datamonitor Healthcare, a market analysis and business information company. “At the moment, I personally find it hard to see CTL019 at the front line of ALL therapy because that’s a disease where a significant portion of patients can be cured with traditional chemotherapy despite nasty side effects,” said Hedden. “CTL019 is likely going to be prohibitively expensive to be used somewhere like that, and then along with that drug there are the safety elements. Specifically for CTL019, even though they can get around these things, it is going to push it further to the back of the treatment algorithm, where patients have exhausted other options.”

That said, if oncologists could manage CRS better and improve patients’ response to CAR-adjusted cells, the treatment could be among the tools doctors turn to first when dealing with leukemia, Hedden said.

Hedden gives a rough estimate of $100,000 to $350,000 for a complete CAR treatment, based on industry discussion and using as a baseline the $93,000 cost in 2010 for a full treatment of Provenge. If the price of CAR treatment soars too high, manufacturers could be hard pressed to recoup their investment, he said.

“Could it push out first-line drugs? I don’t think so. I don’t think insurers are going to want to pay when other treatment options are available,” said Hedden.

At the same time, he said that success with CAR strategies against solid tumors could open up vastly lucrative markets.

Azam declined to put a figure on the cost of CAR treatment for ALL. “I think it’s premature to give a price on what this would cost.” He said the value of the medicine as a potential cure for ALL merits his company’s very bullish stance on development. “You’re looking at other options for patients, which are very scant.”

Oncologists interviewed for this story agreed that chemotherapy could be cheaper in a simple comparison, but they said there are also hidden costs to be weighed. Among them are complications of chemotherapy such as blood transfusions or serious infections, lifelong follow-up care and medication often required as a result of chemotherapy, and bone marrow transplant (BMT) for patients with relapsed disease.

They said insurers could decide that a pound of cure in the form of CAR therapy could be far more cost effective. If a CAR therapy administered early can prevent those patients who would otherwise need a BMT from getting the procedure or perhaps reducing the total amount of chemotherapy needed, the cost savings over the patient’s lifetime could be significant.

“Currently, if your child is diagnosed with ALL, she’d need two years of chemotherapy if you’re a girl and three years if you’re a boy, and at the end of the day have an 85% chance of being cured. But what people don’t understand is that these kids pay a significant price for that,” said Lee.

“Upwards of 30% of childhood ALL survivors have a significant comorbidity that limits their functioning as an adult, and that’s a huge number. So any new therapy that comes along that can potentially reduce the exposure of cytotoxic agents for these kids would be a huge windfall,” said Lee. That’s a financial argument that insurance companies would likely accept, agreed Brentjens of MSK, but he said that before paying for the procedure, they would need to know that CAR therapy is an effective modality.

When Marcela V. Maus, MD, PhD, thinks of the challenge of bringing chimeric antigen receptor (CAR) therapies to market in the battle against cancer, she is reminded of the auto industry's first days. 

Tony Hagen

Articles

COA Says New Care Model Doesn't Go Far Enough

ABIM Rolls Back MOC Changes

Bringing CARs to Market: Novel T-Cell Therapies Make Rapid Progress Despite Challenges