I've been credentialed to cover CHI's Immuno-Oncology Summit in Boston next week

I'm happy to say that I have been registered to attend and cover CHI's Seventh Annual Immuno-Oncology Summit next week in Boston. Immunotherapy was the subject of a fascinating panel at BIO last month. I am available to cover this meeting.

https://www.immuno-oncologysummit.com/programs

ASCO 2019: ASCO Releases First-Ever Guidelines for Multiple Myeloma

Development comes on the heels of new drugs, increased overall survival, and revised diagnostic criteria

By John Otrompke

                Science recently achieved a medical milestone, with the publication of ASCO’s first set of guidelines for the treatment of multiple myeloma on May 10. Four new drugs have been approved since 2015. However, the disease remains incurable, with a median survival of slightly more than five years.

Most patients receive at least four lines of therapy, according to the article, “Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline” (Mikhael, J; Nofisat, I.; Cheung, M; et al). DOI: 10.1200/JCO.18.02096 Journal of Clinical Oncology 37, no. 14 (May 10 2019) 1228-1263.

“Survival in the last 15 years is substantially better,” said Dr. Catherine Diefenbach, MD, director of the clinical lymphoma program at the NYU Langone Perlmutter Cancer Center in New York City. “A study by Kumar et al. (Blood 2008 111:2516-2520) found a clear improvement in overall survival for multiple myeloma patients with relapsed disease after autologous stem cell transplant, with those relapsing 2000 having a median OS of 23.9,  versus 11.9 months for those who relapsed before 2000,” explained Diefenbach, who is also an ASCO committee member.

 Even with Five Year Survival, Disease Still Incurable

Therefore, the guidelines place an emphasis on newer agents; recommendation 5.2, for example, suggests that those patients ineligible for stem cell transplant should receive, at a minimum, a novel agent, and a steroid, if possible.

The guidelines are the result of an analysis of 124 relevant studies.

“The review began in 2005, because the therapies that proceeded this are not relevant to the therapies in use today,” said Diefenbach. “For example, daratumumab is an IgG1kappa monoclonal antibody directed against the antigen CD38 which is highly expressed by multiple myeloma cells,” she explained.

(Daratumumab was given breakthrough status by the FDA in 2013, which put it on an expedited approval schedule. It was also awarded orphan status by the FDA).

                Another new drug is elotuzumab, which received breakthrough status in 2014. “Dartumumab is approved for both upfront therapy of multiple myeloma and for relapsed disease in combination with other agents. Elotuzumab is approved for relapsed patients that have failed one to three lines of therapy in combination with other agents,” Diefenbach noted.

Diagnostic Criteria Updated, Especially for Smoldering Myeloma

                Along with the approval of new agents, the diagnostic criteria were updated by the International Myeloma Working Group (IMWG) in 2014. (Lancet Oncol. 2014 Nov;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5. Epub 2014 Oct 26). “Many patients who would have previously been defined as having smoldering myeloma will now be more appropriately defined as active and in need of therapy,” according to the guidelines published in JCO.

Autologous stem cell transplant for patients in first remission remains the standard of care, and age and renal function should not be the sole criteria for determining eligibility, according to recommendation 1.2.

For those who are ineligible for transplant, or in first remission, triplet therapies should be considered. (A triplet is defined as including two novel agents, according to recommendation 7.3). According to recommendation 5.3, a combination of the four agents daratumumab, bortezomib, melphalan and prednisone can also be considered.

However, continuous therapy should be offered preferentially to fixed-duration treatment when initiating certain novel agents, such as an immunomodulatory drug or a proteasome inhibitor, according to recommendation 5.5.

“Acquired mutations are important for the progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma, but have less significance for disease progression in multiple myeloma,” said Diefenbach. (MGUS is also known as smoldering myeloma). However, “most multiple myeloma patients will relapse and become resistant to therapy over time,” she added.

                Genetic markers for high-risk disease include cytogenetic abnormalities such as t(4;14), t(14;16), t(14;20), del17p13.

Several conferences I am already scheduled to cover this fall

Hi, here are several conferences I have already made arrangements to cover this fall.

They include the Heart Failure Society, AACAP, ACS, RSNA, and the American Epilepsy Society.

Is anyone else interested in articles from these meetings? If so, I need charge you no expenses.

Many thanks,

~John
John_Otrompke@yahoo.com


1. Heart Failure Society of America
Sept. 13-16, Philadelphia
https://meeting.hfsa.org/<https://meeting.hfsa.org/>

2. American Academy of Child and Adolescent Psychiatry
Oct 14-19, Chicago
https://www.aacap.org/AACAP/CME_and_Meetings/Annual_Meeting/66th_Annual_Meeting/66th_AM_Home.aspx<https://www.aacap.org/AACAP/CME_and_Meetings/Annual_Meeting/66th_Annual_Meeting/66th_AM_Home.aspx>

3. American College of Surgeons
Oct 27-31, San Francisco
https://www.facs.org/clincon2019<https://www.facs.org/clincon2019>

4. Radiological Society of North America
Dec 1-6, Chicago
https://www.rsna.org/annual-meeting<https://www.rsna.org/annual-meeting>

5. American Epilepsy Society
Dec. 6-10, Baltimore
https://meeting.aesnet.org/<https://meeting.aesnet.org/>

Pharma DJ published my article on FDA Commissioner Norman Sharpless from this year's BIO conference

My new client, PharmaDJ (based in Shanghai, China) published my article from the annual BIO conference last month, describing a townhall held by the on FDA Commissioner Dr. Norman Sharpless.

US FDA Must Hire New Staff to Fulfill New Obligations and Review New Technologies

June 12, 2019

http://www.pharmadj.com/cms/detail.htm?item.id=6672f4078cb711e98efdfa163e227c38

Pediatric Phase 1 Dose-Finding Study of Entrectinib Shows Substantial Benefit in Almost Half the Patients

by John Otrompke

A second study in pediatric oncology discussed at the ASCO presscast also was the source of surprisingly good news.

STARTRK-NG was designed as a simple phase I/IB dose-finding study, but objective responses were seen in almost half of the subjects. The study enrolled 29 patients, aged 4 to 20, with rare central nervous system tumors, neuroblastoma, or other solid tumors, of whom 28 were evaluable.

Entrectinib, a novel targeted treatment, was administered for a median of 281 days, and the tumor shrank or disappeared in 12 patients. The median time to response was 57 days, according to abstract 10009, “Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors” (Robinson, Gajjar, Gauvain, et al).

“The medicine was well-tolerated and there appears to be no time frame yet studied in which the medicine stops working or toxicities become limiting,” according to lead author Giles W. Robinson, MD, a pediatric neuro-oncologist at St. Jude Children's Research Hospital in Memphis, who was quoted in the ASCO press release.

No responses were observed among patients lacking the alterations targeted by entrectinib.

Therapies potentially available in the Pediatric MATCH trial, and the mutations they target

• larotrectinib- targeting NTRK

• erdafitinib- targeting FGFR

• tazemetostat- targeting EZH2 and other SWI/SNF complex genes

• LY3023414- targeting the PI3K/MTOR pathway

• selumetinib- targeting the MAPK pathway

• ensartinib- targeting ALK or ROS1

• vemurafenib- targeting BRAF

• olaparib- targeting defects in DNA damage repair

• palbociclib- targeting cell cycle genes

• ulixertinib- targeting the MAPK pathway

Targeted Therapies May Play a Greater Role in Pediatric Oncology

by John Otrompke

                A study attempted to match pediatric cancer patients with genomic treatments has been more successful than predicted, according to a presentation at the pre-meeting press cast of the American Society for Clinical Oncology (ASCO) given on May 15.

                At the outset of the project (the National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice, or NCI-COG Pediatric MATCH) in 2017, researchers predicted that only 10% of children with refractory cancer would have a mutation-based match to genomic treatment, according to COG study chair Will Parsons, MD, PhD, associate professor of pediatrics-oncology at Baylor College of Medicine in Houston.

But an interim analysis of more than 400 patients screened has revealed a significantly higher match rate, with 24% of participants eligible to receive treatment with at least one drug, according to the ASCO press release.

“The last 10 years has been an incredible time,” said Parsons, who spoke at the presscast, discussing abstract 10011, “Identification of targetable molecular alterations in the NCI -COG Pediatric MATCH trial” (Parsons, Janeway, Patton, et al).

The median turn-around time was 15 days. But while 24% of enrollees had a match to an eligible treatment, only 10% (39 patients) had actually enrolled in a Pediatric MATCH treatment trial, according to the press release.

Children with cancer sometimes have a better prognosis than adults, yet fewer targeted therapies for cancer are tested in children than adults. (There are more than 150 U.S. approvals for targeted therapies in adult cancers). This situation led ASCO to identify research into precision therapies in pediatric cancers as a priority.

While the abstract presented at the presscast discussed the results of the Pediatric MATCH screening trial, there is also a treatment protocol, Parsons said.