Lymphomatoid Granulomatosis

WEDNESDAY, April 12, 2023 -- For low-grade lymphomatoid granulomatosis, interferon alfa-2b is efficacious, according to a study published online March 31 in The Lancet Haematology . Christopher Melani, M.D., from the National Institutes of Health in Bethesda, Maryland, and colleagues enrolled 67 patients aged 12 years or older with untreated, relapsed, or refractory lymphomatoid granulomatosis. Patients with low-grade disease received dose-escalated interferon alfa-2b, and those with high-grade disease received six cycles of intravenous, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). After initial therapy, patients with residual or progressive disease crossed over to alternative therapy. Forty-five patients received initial treatment with interferon alfa-2b (16 crossed over to DA-EPOCH-R) and 18 received initial treatment with DA-EPOCH-R (eight crossed over to interferon alfa-2b); four only received surveillance. The researchers found that the overall response was 64 percent after initial treatment with interferon-alfa-2b (61 percent had complete response), while the overall response was 63 percent (50 percent with complete response) after cross-over treatment with interferon alfa-2b. The overall response rate was 76 percent after initial treatment with DA-EPOCH-R (47 percent had complete response), while the overall response was 67 percent (47 percent with complete response) after cross-over treatment with DA-EPOCH-R. Five-year progression-free survival was 48.5, 50.0, 25.4, and 62.5 percent, respectively, with initial treatment with interferon alfa-2b, cross-over treatment with interferon alfa-2b, initial treatment with DA-EPOCH-R, and cross-over treatment with DA-EPOCH-R, respectively. "We have shown in this rare disorder that using a novel immunotherapy-based approach for low-grade disease is effective and improves survival compared with historical treatments such as chemotherapy and corticosteroids," Melani said in a statement. One author disclosed financial ties to the biopharmaceutical industry. Abstract/Full Text (subscription or payment may be required) Editorial (subscription or payment may be required) Posted April 2023

April 4, 2023 -- Results from a clinical trial conducted by researchers at the National Institutes of Health (NIH) show that people with low-grade lymphomatoid granulomatosis who are treated with interferon alfa-2b, a type of immunotherapy, can live for decades after diagnosis. Lymphomatoid granulomatosis is a rare precancerous condition triggered by Epstein-Barr virus infection. Left untreated, the disease can progress to a high-grade form, which has a poorer prognosis and can quickly turn into an aggressive and fatal B-cell lymphoma. In the phase 2 trial, led by researchers in the Center for Cancer Research at the National Cancer Institute (NCI), part of NIH, patients treated with interferon alfa-2b lived for a median of about 20 years. By contrast, past studies reported a median survival of less than two years for people with lymphomatoid granulomatosis. The findings suggest that immunotherapy can prevent the progression of low-grade disease to high-grade disease. The results were published March 31, 2023, in Lancet Haematology . “We have shown in this rare disorder that using a novel immunotherapy-based approach for low-grade disease is effective and improves survival compared with historical treatments such as chemotherapy and corticosteroids,” said Christopher J. Melani, M.D., of NCI’s Center for Cancer Research, who co-led the study. “I think the results of this study represent a significant contribution to determining the standard-of-care treatment for this rare disease.” Lymphomatoid granulomatosis causes an overproduction of white blood cells known as B lymphocytes. Patients typically have lesions in the lungs, central nervous system, skin, liver, and kidneys. Symptoms can include cough, shortness of breath, fever, weight loss, and fatigue. Chemotherapy is currently the standard treatment for people with high-grade disease, but there is no standard treatment for low-grade disease. “Although lymphomatoid granulomatosis is uncommon, the effects of high-grade disease can be debilitating,” said Jeffrey Cohen, M.D., chief of the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases and a co-leader of the study. “We need better ways to prevent the disease from progressing to this more severe state, such as interferon alfa-2b.” NIH researchers have been studying lymphomatoid granulomatosis since the 1980s. In the early 1990s, Wyndham Wilson, M.D., Ph.D., also of NCI’s Center for Cancer Research, hypothesized that low-grade disease results from a defective immune response to the Epstein-Barr virus and could therefore be treated with immunotherapy, whereas high-grade disease requires chemotherapy to curb uncontrolled cell growth. He and his colleagues treated four people with low-grade lymphomatoid granulomatosis with interferon alfa-2b over a 5-year period, and the treatment eradicated all signs of the disease in three of those patients, known as a complete remission. That study laid the foundation for the phase 2 trial of interferon alfa-2b in lymphomatoid granulomatosis, which has taken 30 years to complete because of the rarity of the disease and the challenges of recruiting enough patients for the study. “This really illustrates the unique ability of NIH to do a study like this that nobody else could do and no one else ever has done for this particular disease,” said Dr. Wilson, who co-led the study. The trial included 67 people with lymphomatoid granulomatosis, 37 with low-grade disease and 30 with high-grade disease. In all cases, the participants had not yet been treated for the disease or their disease had not responded to or had returned after other treatments. During their initial treatment, most of the patients with low-grade disease received subcutaneous injections of interferon alfa-2b three times a week in increasing doses for about one year. Most of the patients with high-grade disease were given six cycles of intravenous chemotherapy every three weeks. Both groups improved, with the disease disappearing in 27 of 44 patients (61%) treated with interferon alfa-2b, and 8 of 17 patients (47%) treated with chemotherapy. After their initial treatment, some patients subsequently received the other therapy, called crossover treatment. Patients with low-grade disease that worsened after immunotherapy were given chemotherapy, whereas patients with high-grade disease that came back after chemotherapy were given interferon alfa-2b. Previous work showed that after high-grade disease is eliminated with chemotherapy, low-grade disease can re-emerge. The crossover treatments were also effective, with the disease disappearing in 4 of 8 patients (50%) treated with interferon alfa-2b after chemotherapy and 7 of 15 patients (47%) treated with chemotherapy after interferon alfa-2b. Median overall survival was 20.6 years for patients treated initially with interferon alfa-2b and 19.8 years for patients who crossed over to receive interferon alfa-2b. Median overall survival was 12.1 years for patients treated initially with chemotherapy and not reached for those who crossed over to receive chemotherapy. The most common side effect of interferon alfa-2b treatment was low white blood cell count, and the most common side effects with chemotherapy were low white blood cell count and infection. Serious side effects occurred in only a quarter of the patients treated with interferon alfa-2b, compared with nearly two-thirds of patients treated with chemotherapy. Many newer immunotherapies, such as nivolumab, could potentially be used to treat low-grade lymphomatoid granulomatosis and other Epstein-Barr virus–associated disorders and may have fewer side effects. “The trial of interferon alfa-2b established that immunotherapy improves survival in patients with low-grade lymphomatoid granulomatosis,” Dr. Melani said. “Now we can look into more novel immunotherapies that are easier to tolerate to see if they can improve on the efficacy of our current treatment.” The study was funded by the intramural research programs of NCI and the National Institute of Allergy and Infectious Diseases. About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of people with cancer. NCI supports a wide range of cancer research and training extramurally through grants and contracts. NCI’s intramural research program conducts innovative, transdisciplinary basic, translational, clinical, and epidemiological research on the causes of cancer, avenues for prevention, risk prediction, early detection, and treatment, including research at the NIH Clinical Center—the world’s largest research hospital. Learn more about the intramural research done in NCI’s Center for Cancer Research. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center at 1-800-4-CANCER (1-800-422-6237). About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov . NIH…Turning Discovery Into Health ® Source: NIH Posted: April 2023

-- Results from this ongoing, noninterventional rollover study were presented at the 23rd Annual Society of Urological Oncology (SUO) Meeting in San Diego SAN DIEGO--(BUSINESS WIRE)-- UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, today announced new data from the OPTIMA II study designed to obtain long-term follow-up data on UGN-102 that shows median duration of response (DOR) of 24.4 months for UroGen’s investigational drug UGN-102 currently in Phase 3 development for low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The study (Abstract #193) was presented at SUO on December 2. “LG-IR-NMIBC is a challenging disease to treat because of the high recurrence rate managed by repetitive surgeries,” says William C. Huang, M.D., FACS, Professor and Vice Chair of Urology at NYU Langone Health and Principal Investigator of the OPTIMA II trial. “The OPTIMA II Phase 2b trial showed significant tumor response benefit for patients using the novel chemoablative therapy UGN-102 for LG-IR-NMIBC and this latest analysis shows that the treatment benefit lasted for more than two years. I look forward to additional data on UGN-102, including evidence from the ENVISION Phase 3 study.” Patients who completed the OPTIMA II study were eligible to participate in this rollover study. Outcomes include DOR in patients who remained in complete response (CR) at the end of OPTIMA II, events of disease recurrence and progression, post-study treatments and death. At the time of data cut off (February 25, 2022), data were available for 15 of the 25 patients. The median DOR among the 15 patients was 24.4 months (10.1 to 30.7 months). Seven patients remained in CR, six patients had recurrence of LG disease, one patient had progression to high-grade disease and one patient withdrew consent (no longer mobile) but remained in CR at the last evaluation prior to discontinuation. All patients were alive at the last contact, and five patients were known to have had post-study treatment with transurethral resection of the bladder tumors (three patients) or fulguration (two patients). DOR was calculated as the time from documented CR in OPTIMA II to disease recurrence or death or last adequate disease assessment (for patients who remained in CR). The data cut off for this report is February 25, 2022. “UGN-102 uses a similar combination with a simpler delivery method to our currently approved chemoablative medicine and has showed a similar durability of response in LG-IR-NMIBC,” said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. UroGen’s proprietary RTGel™ technology allows medicines to dwell for several hours potentially improving the therapeutic effects of existing medicines. If approved, UGN-102 would be the only primary non-surgical treatment option for patients with LG-IR-NMIBC who often recur within one year of receiving surgery and continue to need repetitive surgeries for the rest of their life.” About the Phase 2b OPTIMA II Trial OPTIMA II (OPTimized Instillation of Mitomycin for Bladder Cancer Treatment) is an open-label, single-arm, multi-center Phase 2b clinical trial of investigational agent UGN-102 (mitomycin) for intravesical solution to evaluate its safety and efficacy in patients with LG-IR-NMIBC. Results showed: 65 percent CR at three months Kaplan-Meier analysis estimated duration of response to be 72.5 percent at 12 months from initiation of therapy (nine months from CR); median duration of response was not reached Treatment with UGN-102 was generally well tolerated, with mostly mild to moderate adverse events reported Intermediate risk is defined as one or two of the following: multiple tumors, solitary tumor >3 cm, or recurrence (≥ 1 occurrence of LG-NMIBC within one year of the current diagnosis). Patients were to receive six weekly intravesical instillations of 75 mg UGN-102 in an office setting. The chemoablative effect of UGN-102 was assessed three months after initiation of study treatment with CR defined as a negative endoscopic examination, negative cytology, and when indicated, a negative for-cause biopsy. Patients achieving CR were followed quarterly to 12 months after initiation of study treatment to evaluate safety, efficacy, and durability. About LG-IR-NMIBC Approximately 800,000 people are living with bladder cancer in the U.S., of that 80,000 suffer from LG-IR-NMIBC. Patients with LG-IR-NMIBC face a future of recurrence and additional surgeries. Currently, the only primary treatment available is a surgical procedure known as transurethral resection of bladder tumor or TURBT, which requires anesthesia. Every time TURBT is performed it may impose more burden and serious risks on patients, including pain, bleeding, infection and injury (including perforation). About UroGen Pharma Ltd. UroGen is biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers because patients deserve better. UroGen has developed RTGel™ reverse-thermal hydrogel, a proprietary sustained release, hydrogel-based platform technology that has the potential to improve therapeutic profiles of existing drugs. UroGen’s sustained release technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option. UroGen’s first commercial product JELMYTO (mitomycin) for pyelocalyceal solution, and investigational treatment UGN-102 (mitomycin) for intravesical solution for patients with low-grade non-muscle invasive bladder cancer, are designed to ablate tumors by non-surgical means. UroGen is headquartered in Princeton, NJ with operations in Israel. Visit to learn more or follow us on Twitter, @UroGenPharma. Forward-Looking Statements This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the ongoing non-interventional, rollover study of UGN-102; the ongoing ENVISION Phase 3 trial; the potential of UroGen’s proprietary RTGel technology platform to improve therapeutic profiles of existing drugs; the potential benefits of UGN-102 for the treatment of LG-IR-NMIBC and UroGen’s sustained release technology making local delivery potentially more effective as compared to other treatment options. These statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: results from initial reports of long term follow-up outcomes may not be indicative of results that may be observed in future clinical practice; the timing and success of clinical trials and potential safety and other complications thereof, including the ENVISION Phase 3 trial; the ability to obtain regulatory approval within the timeframe expected, or at all; the ability to maintain regulatory approval; complications associated with commercialization activities, including complications resulting from the COVID-19 pandemic; the labeling for any approved product; competition in our industry; the scope, progress and expansion of developing and commercializing UroGen’s product candidates; the size and growth of the market(s) therefor and the rate and degree of market acceptance thereof vis-à-vis alternative therapies. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of UroGen’s Form 10-Q filed with the SEC on November 10, 2022 and other filings that UroGen makes with the SEC from time to time (which are available at ), the events and circumstances discussed in such forward-looking statements may not occur, and UroGen’s actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to UroGen as of the date of this release.