Approaching Treatment of Relapsed/Refractory Myeloma

Keith Stewart, MD, ChB, MBA, Mayo Clinic, Sagar Lonial, MD, FACP, Winship Cancer Institute, Cristina Gasparetto, MD, Duke Cancer Institute, Joseph Mikhael, MD, Translational Genomics Research Institute, Nina Shah, MD, UCSF Helen Diller Family Comprehensive Cancer Center. Factors to consider when approaching therapy selection for patients with multiple myeloma disease...
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Unveiling the Nottingham Inversion Instability during the thermo-field emission from refractory metal micro-protrusions

The electron emission by micro-protrusions has been studied for over a century, but the complete explanation of the unstable behaviors and their origin remains an open issue. These systems often evolve towards vacuum breakdown, which makes experimental studies of instabilities very difficult. Modeling studies are therefore necessary. In our model, refractory metals have shown the most striking results for discontinuities or jumps recorded on the electron emitted current under high applied voltages. Herein, we provide evidence on the mechanisms responsible for the initiation of a thermal instability during the field emission from refractory metal micro-protrusions. A jump in the emission current at steady state is found beyond a threshold electric field, and it is correlated to a similar jump in temperature. These jumps are related to a transient runaway of the resistive heating that occurs after the Nottingham flux inversion. That causes the hottest region to move beneath the apex, and generates an emerging heat reflux towards the emitting surface. Two additional conditions are required to initiate the runaway. The emitter geometry must ensure a large emission area and the thermal conductivity must be high enough at high temperatures so that the heat reflux can significantly compete with the heat diffusion towards the thermostat. The whole phenomenon, that we propose to call the Nottingham Inversion Instability, can explain unexpected thermal failures and breakdowns observed with field emitters.
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Loncastuximab Tesirine ‘Could Change Practice’ for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Loncastuximab tesirine produced durable responses in heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to data published in The Lancet Oncology.1. Loncastuximab tesirine is a CD19-directed antibody-drug conjugate that previously showed antitumor activity in a phase 1 study of patients with non-Hodgkin lymphoma.2. In the...
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Options for Second-Line Treatment in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Dr Laurie Sehn reviews the NCCN guidelines for second-line therapy in relapsed/refractory diffuse large B-cell lymphoma and discusses the clinical trial data for a recently approved new treatment combination. Laurie Sehn, MD: What about patients with relapsed/refractory disease? What are their treatment options? We’re talking about a man who’s not...

Zanubrutinib Appears to Elicit Promising Activity in Relapsed/Refractory MCL

Patients with relapsed/refractory mantle cell lymphoma experienced promising response rates after undergoing treatment with zanubrutinib. Zanubrutinib (Brukinsa) yielded positive response rates and demonstrated tolerability in patients with relapsed/refractory mantle cell lymphoma (MCL), according to the results of a phase 1/2 study (NCT02343120) published in Blood Advances.1. Data from the trial...

Carfilzomib Therapies Effective for Patients With Relapsed/Refractory Multiple Myeloma

Treatment with carfilzomib combination therapies are mostly feasible for patients with relapsed/refractory multiple myeloma (RRMM), but further strategies that can overcome bortezomib or lenalidomide resistance are still needed, according to research published in Cancer Reports. Resistance to bortezomib or lenalidomide is strongly associated with failure to first-line therapy, and may...
Diseases & Treatmentstargetedonc.com

Management of Steroid-Refractory Chronic GVHD

Dr Yi-Bin Chen reviews treatment options for patients with steroid-refractory chronic GVHD. Yi-Bin Chen, MD: In chronic graft versus host disease, historically, the treatment options were quite similar. We felt that we just had to suppress the donor immune system, and a lot of patients, again, suffered from opportunistic infection. We need to realize for chronic graft versus host disease, that by the time we treat it, there is some irreversible damage, and we should try to only reverse what we can reverse and shape our expectations for ourselves and our patients that way. But after steroids, we do have an agent that was approved, which is ibrutinib. That's a Bruton tyrosine kinase (BTK) inhibitor, which targets the B-cell arm in the immune system. There is evidence that the B-cell arm is active in many patients with chronic graft versus host disease. A lot of exciting laboratory work had shown in male recipients with female donors the formation of these anti H-Y antibodies directed against the Y chromosome, at least showing there was some B-cell or plasma cell activity. Ruxolitnib has been shown to be quite active in chronic graft versus host disease as well, and we're fairly impressed with that and use it very routinely for that indication. There is an agent called belumosudil, made by Kadmon, that recently had exciting results in the ROCKstar (KD025-213) clinical trials that we hope to see approval for this year. And that targets that ROCK (Rho-associated coiled kinase), an arm thought to be active in fibrosis. And there are other clinical trials ongoing, studying different pathways; a lot of it in chronic graft versus host disease is focused on fibrosis. That is the pathological hallmark we see.

Regimen Deemed Safe, Effective as Bridge to Transplant in Relapsed/Refractory Classical Hodgkin Lymphoma

A second-line chemo-immunotherapy regimen was a “highly effective” bridge to transplant in patients with relapsed or refractory classical Hodgkin lymphoma (cHL), researchers reported in the Journal of Clinical Oncology. The researchers conducted a single-arm, phase 2 study (ClinicalTrials.gov Identifier: NCT03618550) to evaluate the safety and efficacy of the regimen —...

Ruxolitinib Improved Overall Response in the Treatment of Glucocorticoid-Refractory or -Dependent Chronic GVHD

Compared with a control therapy, ruxolitinib increased overall response and improved failure-free survival for patients with glucocorticoid-refractory or -dependent chronic graft-versus-host disease. Using ruxolitinib (Jakafi) to treat patients with glucocorticoid-refractory or -dependent chronic graft-versus-host disease (GVHD) led to a significantly increased overall response, failure-free survival, and symptom response compared with...
Medical & Biotechdrugdiscoverytrends.com

Tazverik gaining momentum

FDA has approved TAZVERIK from Epizyme for multiple indications. The first-in-class EZH2 inhibitor is now indicated for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. The drug is also indicated for adults with relapsed or refractory follicular...

Xospata met primary endpoint in confirmatory trial

In March, Astellas announced that the drug met its primary endpoint in a planned interim analysis of a Phase 3 confirmatory trial for patients with relapsed or refractory FLT3 mutation-positive (FLT3mut+) acute myeloid leukemia (AML). The study, known as COMMODORE, is comparing Xospata to salvage chemotherapy in adult patients. Overall,...

Loncastuximab Tesirine Yields Durable Responses in Patients With Relapsed/Refractory MCL and Other B-Cell NHL Subtypes

Early-phase data indicate that loncastuximab tesirine-lpyl elicited promising, long-lasting responses in patients with mantle cell lymphoma. The antibody-drug conjugate loncastuximab tesirine-lpyl (Zynlonta) as single-agent therapy elicited durable tumor responses in patients with relapsed/refractory mantle cell lymphoma (MCL) and other subtypes of B-cell non-Hodgkin lymphoma (B-NHL), according to the final results of a phase 1 study (NCT02669017).1.

Avelumab Doesn’t Improve Survival in Platinum-Refractory Ovarian Cancer

Treatment with avelumab, either alone or in combination, did not improve survival over standard therapy in patients with platinum-resistant or -refractory ovarian cancer, according to study results published in The Lancet Oncology. In the JAVELIN Ovarian 200 trial (ClinicalTrials.gov Identifier: NCT02580058), researchers compared avelumab monotherapy, avelumab in combination with pegylated...

Cannabis May Help Reduce Refractory Chemotherapy-Induced Nausea

According to the World Cancer Research Fund, as many as 18 million people were diagnosed with cancer worldwide in just 2018 alone. It’s a very sad statistic, and will never quantify the pain and suffering that cancer patients have to endure. Unfortunately, there is no cure for cancer. Cancer comes...