Day: July 4, 2024

Frederick Locke, MD, a medical oncologist and translational researcher in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, explains the allogeneic CD19-directed chimeric antigen receptor (CAR) T-cell therapies, ALLO-501 and ALLO-501A, and how the work. An investigation of ALLO-501 for the treatment of patients with large B-cell lymphoma is occurring in the phase 1 ALPHA study (NCT03939026), which aims to include 74 patients. Patients in the study will be treated with ALLO-501 in addition to ALLO-647 and lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide. The key end point being assessed in the study include dose-limiting toxicity of ALLO-501 and ALLO-647. ALLO-501A is an identical drug to ALLO-501, says Locke. The one difference between the agents is that ALLO-501A has no rituximab (Rituxan) kill switch. Both agents have a gene editing component, which allows for each agent to be used in combination with chemotherapy and a CD52-directed CAR T product, according to Locke. Transcript: 0:08 | ALLO-501 and ALLO-501A are off-the-shelf allogeneic CD19-directed CAR T-cell therapies. The only difference between ALLO-501 and ALLO-501A is that ALLO-501A has removed a rituximab kill switch, which was present in ALLO-501. Otherwise, they’re identical. These CAR T cells have gene editing. So, not only do they express the CD19 CAR, but their gene-edited. The track locus is removed so that the T cell receptor is not expressed and therefore, the cells are unlikely to cause graft-versus-host disease. 0:56 | The CAR T cells are gene-edited so that CD52, which is a cell surface protein that’s on immune cells, is removed from the CAR T cells and that actually allows us to also give an antibody against CD52 as part of the conditioning chemotherapy regimen, which ALLO-647. It’s a monoclonal antibody against CD52, which has been removed from those CAR T cells.

In early 2023, I had my first-ever colonoscopy. I was 68. My wife had been pushing me to get one for several years, but I felt fine and didn’t have any symptoms, so I didn’t think I needed one. To make her happy and to give myself peace of mind, I finally decided to schedule the colorectal cancer screening. The hardest part for me was drinking the bowel prep. The procedure itself was easy; it just felt like a great nap. But when I woke up, my doctor said that he had found a tumor and it was likely cancerous. A CT scan confirmed that I had a tumor, but it didn’t appear to have spread. My wife advised me to make an appointment at MD Anderson. I hesitated because of the distance between Houston and our home in Brownsville, Texas. I’m a college professor, and I felt like I wouldn’t have time for the travel. But my wife told me, “You’ve got the finest cancer hospital up the road. Go.” I knew she was right, so I called and made an appointment. Colorectal cancer surgery at MD Anderson From the moment I first walked into MD Anderson West Houston, I was so impressed. The hospital was beautiful, welcoming and technologically advanced. Even the architecture made me feel like I had walked into the future, which gave me a sense of calm. I knew I was in the right place. I had my first appointment with a colorectal surgeon. What struck me about the doctors and nurses at MD Anderson was their empathy – they listened more than they talked. They told me with confidence that I was going to be fine. Additional imaging confirmed my diagnosis: sigmoid adenocarcinoma. In March 2023, I had laparoscopic surgery at MD Anderson’s Texas Medical Center Campus to remove the tumor. I was able to avoid an ostomy bag because of the tumor’s location. I recovered quickly from surgery. The surgery was in the morning and by that evening I was walking around on my floor of the hospital. Within a week, I was able to drive my wife and myself back home and was shocked to feel quite normal. Teaching my students about the importance of colonoscopies During surgery, my surgeon discovered that the tumor had penetrated the wall of my colon and that a few lymph nodes were affected. This meant the cancer was stage III. To make sure there weren’t any remaining cancer cells, it was recommended I also undergo chemotherapy. Kaysia Ludford, M.D., has coordinated my chemotherapy treatments with a local doctor so I can be closer to home. I started a FOLFOX chemotherapy regimen in June. It hasn’t been easy, and I’ve realized I need to rest for a few days after treatment. The current plan is for me to receive chemotherapy through October. I get an infusion every three weeks and take pills at home on a schedule of two weeks on and one week off. I know that colon cancer is showing up in younger people, so I tell my students to not make the mistake I did and put off getting a colonoscopy. My surgeon told me I’d likely had this tumor for many years. If I’d gotten a colonoscopy earlier, I might have avoided all of this. Request an appointment at MD Anderson online or by calling 1-877-632-6789.

Today I am going to go over what I picked up from the American Hospital Association’s (AHA’s) Coding Clinic for the second quarter of 2023. It was chock-full of interesting advice. Two weeks ago, I went over COVID-19 screening. I think Coding Clinic should have explained why we continue to use Z20.822, Contact with and (suspected) exposure to COVID-19 after May 11, instead of just noting that “this advice is consistent with current coding guidance.” In theory, once there is no longer an epidemic or pandemic, we should be using “contact with” and “suspected exposure” only when we recognize that is the probable scenario. In practice, they are setting the timeline as the end of the fiscal year in which the pandemic ended (that is, 2023). I learned a new code in my review! There is a code, R97.21, Rising PSA following treatment for malignant neoplasm of prostate. This offers a solution on how to code biochemically recurrent prostate cancer, post-prostatectomy, and salvage radiation therapy. The Coding Clinic indicated that, since the prostate had been resected, the culprit has to be a metastasis, and since the site is unknown, you can use C79.9, Secondary malignant neoplasm of unspecified site. My new code is also used because that was how they diagnosed it – that is what “biochemically recurrent” means. A question was posed regarding a patient getting a workup for a suspected malignancy, when an excisional biopsy of a supraclavicular lymph node revealed metastatic non-small cell lung cancer. The question related to the sequencing of the primary and secondary malignancies. Although the procedure is ostensibly linked to the secondary malignancy, the primary malignancy is the condition responsible for both the metastasis and the overall workup/hospital admission. The response is to sequence the primary lung cancer as principal diagnosis (PDx). One should only sequence metastasis as PDx if it is the only focus for diagnostic or therapeutic treatment. An interesting question was asked about venous thoracic outlet syndrome causing left upper extremity swelling and acute left subclavian deep vein thrombosis. The indexing led to G54.0, Brachial plexus disorders, but the questioner proposed I87.1, Compression of vein, as a more accurate clinical representation. The reviewer agreed that since the pathology involved the vein, not nerves, further research should lead the coder to I87.1. To my clinician brain, “compression” usually indicates external forces impacting on the anatomy, like a tumor pressing on the trachea. However, ICD-10-CM indexes kink, obstruction, stenosis, and stricture to “compression of vein,” too. On page 10, there is a question about a patient with pre-existing Type 2 diabetes presenting with hyperglycemia believed to be secondary to autoimmune diabetes after initiation of immunotherapy medication. The answer was to use only E11.65, Type 2 DM with hyperglycemia and T45.1X5A, Adverse effect of antineoplastic and immunosuppressive drugs, initial encounter, for the exacerbation of the disorder of sugar metabolism. I couldn’t help but wonder – where would you go if there were no underlying, pre-existing Type 2 diabetes? In that case, the diabetes code would be E09.65, Drug or chemical induced diabetes mellitus with hyperglycemia. Page 15 features a question about a post-abortion complication. A patient presents for an elective termination of pregnancy due to a genetic abnormality and sustains uterine atony and hemorrhage. If there were a post-abortion code analogous to O72.1, Other immediate postpartum hemorrhage, that would be the right choice. However, since there is not, the advice is to use O04.6, Delayed or excessive hemorrhage following (induced) termination of pregnancy, plus the code for the maternal care for the chromosomal abnormality. Currently, there is an Excludes1 note at O04 precluding concomitant use of Z33.2, Encounter for elective termination of pregnancy, but this will become an Excludes2 on Oct. 1. For this particular code, it makes sense, because excessive hemorrhage could occur at the time of the encounter for the termination (or could be delayed until a subsequent visit). My final comment is that the reason why linkage is assumed resulting in the “with” guidance is that the conditions with the assumed causal relationship are commonly associated, not because the ICD-10-CM classification mandates it. It is the other way around; ICD-10-CM acknowledges the near-inevitable relationship between, for instance, hypertension and heart failure, or diabetes and chronic kidney disease, by assuming causality unless specified otherwise. The words “due to” do establish the relationship if the provider documents them (e.g., hypertension due to hyperthyroidism à I15.2, Hypertension secondary to endocrine disorders). Please review the Coding Clinic guidance yourself. There are more nuggets to collect. And I’d like to extend an invitation to all to join me on LinkedIn on Thursday at 1:30 p.m. EST for my next “Ask Dr. Remer.” You can find the link on my company page, Erica Remer, MD, Inc. Hope to see you then.

– Regulatory Designation Includes Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis and Post-Polycythemia Vera Myelofibrosis – – Pivotal Phase 3 Study of Selinexor and Ruxolitinib in Treatment-Naïve Myelofibrosis Initiated in June 2023 – NEWTON, Mass., July 17, 2023 /PRNewswire/ — Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to the development program of selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis. “Fast Track Designation for selinexor highlights its potential to address the unmet medical need in myelofibrosis, an important acknowledgement as we continue our pivotal Phase 3 study,” said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. “Selinexor’s unique mechanism of action, XPO1 inhibition, is a novel and potentially fundamental mechanism in myelofibrosis. We have been highly encouraged by the efficacy and safety data observed to date [in our Phase 1 study] with selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and believe selinexor has the potential to shift the treatment paradigm. We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need.” In June 2023, Karyopharm initiated a pivotal Phase 3 clinical trial (XPORT-MF-034) (NCT04562389) to assess the efficacy and safety of once-weekly selinexor 60 mg in combination with ruxolitinib in JAKi-naïve patients with myelofibrosis. Updated data from the Phase 1 study were presented at the American Association for Cancer Research Annual Meeting 2023, American Society of Clinical Oncology 2023 and European Hematology Association 2023, which showed rapid, deep and sustained spleen responses and robust symptom improvement in patients treated with selinexor 60 mg in combination with ruxolitinib as of the April 10, 2023 cut-off date. Top-line data from the Phase 3 study is expected in 2025. The Company plans to expand its clinical development program in myelofibrosis by investigating selinexor in other JAKi-naïve settings, such as novel combinations, to benefit the greatest number of patients. Fast Track Designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously. Features of Fast Track Designation include frequent interactions with the FDA review team, and if relevant criteria are met, eligibility for Priority Review and Rolling Review. Further information about the Phase 3 study can be found at www.clinicaltrials.gov. About Karyopharm TherapeuticsKaryopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm’s lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer, myelodysplastic neoplasms and myelofibrosis. For more information about our people, science and pipeline, please visit www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with myelofibrosis; and expectations related to the clinical development of selinexor and potential regulatory submissions of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm’s control, that may cause actual events or results to differ materially from Karyopharm’s current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm’s drug candidates, including selinexor and eltanexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm’s drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm’s drug candidate portfolio will result in stock price appreciation. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; Karyopharm’s results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm’s ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm’s competitors for products or product candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm’s business, results of operations and financial condition; and Karyopharm’s ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption “Risk Factors” in Karyopharm’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2023, and in other filings that Karyopharm may make with