A nationally-published, award-winning journalist, Alex Biese joined the CURE team as an assistant managing editor in April 2023. Prior to that, Alex's work was published in outlets including the Chicago Sun-Times, MTV.com, USA TODAY and the Press of Atlantic City. Alex is a member of NLGJA: The Association of LGBTQ+ Journalists, and also performs at the Jersey Shore with the acoustic jam band Somewhat Relative.

Alex Biese

Optimal dosing of Jakafi was associated with improved efficacy and manageable safety in patients with myelofibrosis: © stock.adobe.com

Optimal dosing of Jakafi (ruxolitinib) was associated with improved efficacy and manageable safety in patients with myelofibrosis, according to study findings from the ongoing, observational, multicenter ROMEI study, which were published in the journal, 

 Notably, this is an Italian-based clinical study.

“To ensure optimal treatment with [Jakafi], patients should be started on appropriate [Jakafi] doses and maintain the highest tolerated dose for maximum effectiveness. Patients who received the recommended doses showed a better trend in response. … Timely [Jakafi] treatment results in maximum patient benefits such as spleen size reduction, symptom relief, and improved [overall survival],” co-first author, Dr. Massimo Breccia, and colleagues wrote in the journal.

Overall survival: the time a patient lives, regardless of disease status.

Thrombocytopenia: a low count of platelets. 

Breccia is part of the Department of Translational and Precision Medicine, at Azienda Ospedaliero-Universitaria Policlinico Umberto I Viale del Policlinico, at the Sapienza University, located in Rome, Italy.

The real-world study — meaning it was research conducted outside of a clinical trial setting — analyzed Jakafi dosing patterns and associated clinical outcomes among patients with myelofibrosis over a 12-month period. Notably, the study enrolled 508 adult patients.

The current interim analysis included two groups of patients: 174 who received the expected dose of Jakafi and 132 patients who received lower than the expected dose of Jakafi, with expected doses based on platelet count class.

Researchers noted that 43.7% of patients were started on 20 milligrams of Jakafi twice daily,

20.6% were started on 15 milligrams twice daily, 22.3% on 10 milligrams twice daily and 12% on 5 mg twice daily, with the remaining 1.4% of patients on a different dosage. Researchers found that 43% of patients were started at a lower-than-expected dose of Jakafi, but both groups of patients exhibited a reduction in average daily Jakafi doses over a 12-month period.

In the as-expected dosing group, the mean daily dose during the first month was 36 milligrams a day and then decreased and stabilized with small fluctuations from the second month at 31 milligrams per day to the twelfth month at 25.3 milligrams per day. Contrarily, in the less-than-expected dosing group, the mean daily dose slightly decreased from 20.7 milligrams per day in the first month to 17.6 milligrams per day in the twelfth month.

At week 48, symptom response rates were 40.8% in the as-expected dosing group and 40.9% in lower-than-expected dosing group. However, the former group showed higher spleen response rates at 24 weeks (50% versus 30.2%) and 48 weeks (57.7% versus 45.8%), with median times to response of 3.3 months versus 1.1 months.

Regarding overall survival, 23 (13.2%) and 27 (20.5%) patients in the as-expected and less-than-expected dosing groups had died by time of data cut-off; the estimated overall survival time was not estimable in the former group and 4.7 years in the latter group.

Researchers noted that in both groups, a slight improvement in all dimensions of reported quality of life was observed at 24 and 48 weeks compared with baseline scores.

Concerning safety, side effects were reported in 87.4% and 84.9% of patients, respectively. Common side effects included blood and lymphatic system disorders (63.8%; 51.5%), anemia (50.6.%; 40.9%) and thrombocytopenia (29.9%; 25.8%).

“Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI)” by Dr. Massimo Breccia et al., 

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Articles

The ROMEI study, an Italian-based observational research, evaluated the dosing and efficacy of Jakafi (ruxolitinib) in myelofibrosis patients. Optimal dosing was linked to improved efficacy and manageable safety. The study involved 508 patients, with two groups based on expected and lower-than-expected doses. The as-expected dosing group showed better spleen response rates and overall survival trends. Both groups experienced symptom relief and quality of life improvements. Common side effects included blood disorders, anemia, and thrombocytopenia, with a high incidence in both groups.

Optimal dosing of Jakafi was associated with improved efficacy and manageable safety in patients with myelofibrosis, according to the ROMEI clinical trial.

Optimal Jakafi Dosing Associated With Improved Outcomes in Myelofibrosis

There is currently no strong evidence that additional immune therapy benefits patients with renal cell carcinoma who were treated in the advanced setting: ©  stock.adobe.com.

Among patients who have received immune therapy in the advanced setting for renal cell carcinoma, “at present, there's no great evidence that more immune therapy is of benefit,” Dr. Brian I. Rini explained in an interview with CURE.

Rini is chief of clinical trials at Vanderbilt-Ingram Cancer Center and Ingram Professor of Cancer Research and a professor of medicine at Vanderbilt University in Nashville. He was among the authors of a review of immunotherapy strategies following immune checkpoint inhibitor exposure among patients with renal cell carcinoma that was published in the journal, 

He discussed his and his colleagues’ findings with CURE.

CURE: To begin, can you expand on what you hope patients will take away from this conversation?

: This was a review article, so we were summarizing the current approaches to treating patients with kidney cancer after they have been exposed to immunotherapy. The central idea was that the majority of patients, either in the adjuvant setting or as their initial treatment for advanced disease, receive some form of immunotherapy. Therefore, there is this emerging and growing population of patients who have had prior exposure to immunotherapy. That was the context for asking, "Well, let's examine the treatment options in that circumstance."

So, we first looked at some other diseases, including lung cancer and melanoma, which have some data in this setting. This was to provide context for the reader, outlining what we know about this area in other cancers. We were particularly focused on whether patients should receive more immunotherapy. There have been trials in kidney cancer—initially case reports, then case series, then single-arm trials, and finally randomized trials—investigating this idea of sequential immunotherapy and whether it provides a benefit in kidney cancer. The review article really goes into detail about all that data, laying out for the reader the evidence of benefit of giving patients more than one immunotherapy.

What findings were generated from this research?

The short answer, working backwards from the most recent, largest trials, is maybe. Currently, there's no strong evidence that more immune therapy benefits patients who have already received it in the advanced setting. Two large, randomized trials yielded negative results. However, as is the case with most trials, they don't address every question. Some lingering unanswered questions include the role of a regimen like Yervoy (ipilimumab) and Opdivo (nivolumab) in that setting, as it wasn't tested in these trials. So, we don't have definitive evidence for or against that. Probably the most important factor is that more and more patients are receiving adjuvant Keytruda (pembrolizumab), which is single-agent PD-1 therapy in the adjuvant setting. In the two large negative trials I mentioned, only a very small number of patients had prior exposure to immune therapy in the adjuvant setting.

So, really, one of the major questions in kidney cancer now is: if someone received adjuvant Keytruda, which is the only approved immune therapy, and a year or two later, or whenever their disease worsens despite that therapy, what is the role of further immune therapy? The article discusses this and offers opinions and editorializes about the potential role, but it's truly an unanswered question.

What other unanswered questions remain, in light of everything that you and your colleagues found?

Maybe the final area is novel immune mechanisms. Right now, in kidney cancer, and to my knowledge, in all cancers, the established immune therapies are PD-1 and PDL-1-based therapies, and perhaps CTLA4-based therapies. However, we really don't know the role of novel immune therapies, such as LAG-3 inhibitors or other immunostimulators, in this immune-refractory setting; it simply hasn't been tested. But that remains an unanswered question.

“Immunotherapy Strategies After Immune Checkpoint Inhibitor Exposure in Renal Cell Carcinoma: A Review” by Dr. Giulia Claire Giudice et al., 

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The current evidence suggests limited benefit from additional immunotherapy in renal cell carcinoma patients previously treated with immune checkpoint inhibitors. Two large randomized trials showed no significant advantage of further immune therapy in the advanced setting. Unanswered questions remain regarding the role of regimens like ipilimumab and nivolumab, especially for patients who received adjuvant pembrolizumab. The potential of novel immune mechanisms, such as LAG-3 inhibitors, in immune-refractory settings is yet to be explored. These findings highlight the need for further research to optimize treatment strategies.

There is currently no strong evidence that additional immune therapy benefits patients with renal cell carcinoma who were treated in the advanced setting.

Reassessing Immunotherapy Use in Advanced Renal Cell Carcinoma

Deferring upfront CNS-directed radiation in EGFR-variant and ALK-positive NSCLC may improve outcomes but raises treatment-related toxicity risks: ©  stock.adobe.com

For patients with EGFR-variant and ALK-positive non-small cell lung cancer (NSCLC) with brain metastases, deferring up-front central nervous system-directed radiation therapy has been associated with improved outcomes, but with an increase in treatment-related toxicity, according to recent findings.

Dr. Luke R.G. Pike and colleagues published their findings in a recent article from 

. Pike is a radiation oncologist and director of brain radiation oncology at Memorial Sloan Kettering Cancer Center in New York City.

“In the era of [central nervous system]-active [tyrosine kinase inhibitors], the largest multicenter study to date of patients with EGFR-variant and ALK-positive NSCLC found that up-front [stereotactic radiosurgery] was associated with superior local control and time to [central nervous system] progression at the cost of increased treatment-related toxic effects in a minority of patients. Patients with higher-risk [brain metastases], including those with lesions that are large, symptomatic or located in eloquent areas, may benefit more from early [stereotactic radiosurgery],” Pike and his colleagues wrote in the article.

Pike and his colleagues came to their findings after reviewing three multi-institutional cohort studies from the United States and Japan between 2013 to 2022. These studies comprised 591 patients, 52% of whom were male and who had an age range of 35 to 92 years old. Investigators compared central nervous system-active tyrosine kinase inhibitors with or without radiotherapy.

Contemporary practice guidelines, Pike and his colleagues noted, support the deferral of up-front stereotactic radiosurgery for some patients with EGFR-variant and 

 who have limited, asymptomatic brain metastases.

Given a lack of clear survival benefit, Pike and his co-authors stated that, “based on clinical factors and patient preferences [specific points] appear reasonable in light of the available evidence.” These points include:

Multidisciplinary evaluation and individualized decisions regarding therapeutic intensification, such as early stereotactic radiosurgery delivery as either up-front therapy or as consolidation after patients’ response to tyrosine kinase inhibitors.

Deintensification, such as treatment with tyrosine kinase inhibitors alone, close brain MRI surveillance and early salvage therapy at central nervous system progression.

Looking forward, Pike and his colleagues stated that randomized clinical trials testing a strategy of using central nervous system-active tyrosine kinase inhibitors with or without stereotactic radiosurgery are warranted.

Brain metastases, as the reseach states, have been shown to be a common cause of morbidity and mortality among patients with EGFR-variant and ALK-positive NSCLC. Stereotactic radiosurgery is the current standard of care for limited brain metastases, and it has shown what Pike and his fellow researchers described as “excellent long-term lesion control rates”, although they note that late cerebral radionecrosis, or damage to brain tissue, can be a concern for long-lived and heavily treated patients.

Brain metastases, as explained by the American Lung Association on its website, can occur when cancer cells metastasize, or spread from the original cancer site in the lung, to the brain. Brain metastases may form one or multiple tumors in the brain, and as the metastatic brain tumors grow, they create pressure on parts of brain and they can change the function of surrounding brain tissue, which can cause a range of symptoms.

Management of EGFR-Variant and ALK-Positive Non–Small Cell Lung Cancer Brain Metastasis” by Dr. Luke R. G. Pike et al., 

Recent findings suggest that deferring up-front CNS-directed radiation therapy in patients with EGFR-variant and ALK-positive NSCLC with brain metastases can improve outcomes but may increase treatment-related toxicity. The largest multicenter study to date indicates that up-front stereotactic radiosurgery offers superior local control and CNS progression time, albeit with increased toxic effects. Current guidelines recommend deferring stereotactic radiosurgery for patients with limited, asymptomatic brain metastases. Future randomized clinical trials are needed to evaluate CNS-active tyrosine kinase inhibitors with or without stereotactic radiosurgery.

Deferring upfront CNS-directed radiation in EGFR-variant and ALK-positive NSCLC may improve outcomes but raises treatment-related toxicity risks. 

Radiation Delay in NSCLC May Aid Outcomes, But Raises Toxicity Risks 

Padcev and Keytruda now set the standard for advanced bladder cancer, surpassing older single-agent immunotherapy approaches.

An international team of researchers has published their findings detailing potential predictors of response to immunotherapy among patients with advanced bladder cancer that were determined via a meta-analysis of six independent cohorts of patients.

While researchers, who published their findings in 

, analyzed the data of 466 patients who had received single-agent immunotherapy treatment for advanced, metastatic bladder cancer, “nowadays that’s not the way that we treat bladder cancer,” as study co-author Dr. Joaquim Bellmunt explained.

Bellmunt is an associate professor at Harvard Medical School and director of the Bladder Cancer Center at Genitourinary Oncology Program of Dana-Farber Cancer Institute, both in Boston.

“We have moved ahead, and the landscape has changed,” Bellmunt said in an interview with CURE. “And now, for example, in first line we are using still immunotherapy that is, for example, [Keytruda (pembrolizumab)], the PD-1 inhibitor. But this is combined with a new type of chemotherapy, a personalized or let's say more targeted chemotherapy, that are antibody-drug conjugates.

“And the antibody-drug conjugate that we are giving together with immunotherapy is named 

 It is like a carrier of a payload that is a chemotherapy. And this antibody, that is a carrier, is looking, searching for the cancer cell. The cancer cell is identified because this antibody is detecting or targeting what is called NECTIN-4, that is an antigen highly expressed in tumor cells, and then this antibody arrives to the cancer cell, and the cancer cell engulfs the antibody-drug conjugate, and then the chemotherapy is released inside the cell.”

(FDA) approved the combination of Padcev and Keytruda 

for patients with locally advanced or metastatic bladder cancer in December 2023, less than a year after the regulatory agency granted the drug combination accelerated approval for the treatment of patients who were ineligible for treatment with cisplatin-based chemotherapy.

Regarding patients’ response to single-agent immunotherapy, Bellmunt and his colleagues found that, in addition to tumor mutational burden, enrichment in the APOBEC mutational signature and an abundance of pro-inflammatory macrophages were all major factors that were associated with response, as they noted in their study.

“The antibody-drug conjugate combined with immunotherapy is now the standard of care, so meaning that all these studies that we have published are helpful, but — and this is good news —because we are adding another agent, likely we will need to design new tools to say, well, this combination of [Padcev] and [Keytruda] is getting like a 65% response rate in patients with metastatic disease.

“And then, obviously, we will like to know which patients might need other therapies instead of these combinations. And then obviously we will need to do genomic profiling of these patients that are receiving this combination. And maybe some of these predictors that have been described with single agent immunotherapy are going to prevail, so likely the tumor mutational burden like this going to prevail. But there might be other [predictive factors] that will be overcome with the addition within another agent. And those are predictive factors are no longer to be valid.”

“Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts” by Lilian Marie Boll et al., 

Researchers have identified potential predictors of immunotherapy response in advanced bladder cancer through a meta-analysis of six patient cohorts. The study highlights the evolving treatment landscape, with the FDA-approved combination of Keytruda and Padcev now standard for advanced cases. This combination targets NECTIN-4 antigens on tumor cells, enhancing chemotherapy delivery. Key predictors of response include tumor mutational burden, APOBEC mutational signature, and pro-inflammatory macrophages. As treatment evolves, new predictive tools are needed to optimize therapy selection and improve patient outcomes.

Antibody-drug conjugates combined with immunotherapy have redefined the standard of care for advanced bladder cancer, replacing single-agent treatments.

Alex Biese

Optimal Jakafi Dosing Associated With Improved Outcomes in Myelofibrosis

Reassessing Immunotherapy Use in Advanced Renal Cell Carcinoma

Radiation Delay in NSCLC May Aid Outcomes, But Raises Toxicity Risks

Antibody-Drug Conjugates Changed the Standard of Care in Bladder Cancer

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