PDSA e-News: January 29, 2021

This year’s 62nd ASH Annual Meeting and Exposition was virtual due to the global pandemic. Held December 5-8, the meeting attracted thousands of clinicians, scientists, pharmaceutical company personnel and even investment analysts worldwide to share ground-breaking research in the field of hematology. In conjunction with the ASH meeting, PDSA hosted the annual Friday Morning ITP Breakfast , coordinated by PDSA and four of PDSA’s Medical Advisors, James Bussel, MD, Nichola Cooper, MD, Michele Lambert, MD and John Semple, PhD. This year’s virtual event featured fourteen hematology experts from seven countries who presented their leading-edge ITP research. In this issue of the e-news, we report on research contributed to by PDSA staff and advisors showcasing advanced knowledge on ITP therapies and patients’ overall quality of life living with ITP. Watch for additional ASH reports in the winter issue of The Platelet News, the PDSA quarterly newsletter.


A Multicentre Randomized Trial of First-line Treatment Pathways For Newly Diagnosed Immune Thrombocytopenia: A Standard Steroid Treatment vs Combined Steroid and Mycophenolate (FLIGHT Trial)

test tubes in laboratoryThis study is the first randomized control trial of the combination of corticosteroids and mycophenolate (MFF) as initial therapy for adults with ITP. While corticosteroids are the most commonly used first-line therapy, MMF has generally been used more as an alternative way to treat patients who have not responded to second-line therapies. The drug is relatively inexpensive and is generally well tolerated, even in elderly patients. However, the onset of action is delayed, so the drug has to be administered for weeks to months before a clinical benefit is seen. In this study, the efficacy of the MFF/corticosteroid combination as first-line therapy was compared to corticosteroids alone, which is the current standard of care. Inclusion criteria included ITP patients over the age of 16 years who met criteria for a first-line therapy and had a platelet count under 30,000/µL. In total, 120 patients were included and followed for an average of eighteen months. The average age of the participants was 54 years and the average platelet count was 7,000/µL. Results revealed that initiating treatment with the MFF/corticosteroid combination resulted in 50% fewer treatment failures (22%) compared with corticosteroid alone (44%) (defined as platelet counts under 30,000/ µL and requiring second-line therapy). There was no difference in responses at two weeks, reflecting the slow onset of action of MMF. However, those who received the MMF/steroid combination obtained higher platelet counts and fewer patients were refractory (i.e. no platelet counts > 20,000/µL) to treatment (6.8% in the combination group vs 24.6% in the monotherapy group). Combination therapy was generally well tolerated even with a high number of elderly patients enrolled, i.e. 27.5% of the patients were older than 70 years. Side effects were similar in two groups and were dominated by corticosteroid toxicity, including weight gain, mood disturbances and difficulty sleeping. Bleeding events, utilization of rescue therapy, and hospitalizations were similar in the two groups. Those receiving combination therapy reported more fatigue and physical health issues than the monotherapy group and the general population.


Comments from PDSA’s Medical Advisors:

This is an exciting study. There is evidence emerging from this and other studies that the use of more intensive treatment “up-front” may have a beneficial effect on the later course of the disease. The concern, of course, is that some ITP patients will go into remission with standard measures, there is no way to predict responders to combination therapy, and, of course there is concern about toxicity when more than one drug is employed.

In this study, the use of combining MMF and corticosteroids as first line therapy in adults with ITP reduced the failure rate by half compared with corticosteroids alone and with no serious additional toxicity reported. The failure to improve quality of life with MMF is surprising and the reason is not clear.

This result suggests combining MMF with a short dose of corticosteroids at the onset of treatment might be considered as a first-line therapy option for some adult patients with ITP to shorten their course of steroid therapy and to reduce the number of patients requiring second line therapy. The study did not ascertain whether it mattered if the corticosteroid used was dexamethasone versus prednisone, a decision left up to the treating physician. Also the slow onset of effect of MMF may have lessened the chance of reducing steroid usage in the combination arm. However, much longer follow-up will be needed to see how long the benefit lasts and whether delayed side effects as a result of immunosuppression emerge. Also it is not clear why some aspects of quality of life were reduced with the use of combination therapy, which might or might not relate to the use of MMF. This study is one more step in finding treatment options that reduce reliance on corticosteroids. In addition to establishing durability of response, future investigation should be directed to identifying which patients are in need of and more likely to respond to more intense combination therapy employed in this study.

Decision Aid to Support Shared Decision Making in Pediatric Refractory Immune Thrombocytopenia

doctor with child patientThis study, funded by PDSA, focuses on common reasons patients with refractory immune thrombocytopenia (ITP) seek treatment from the perspective of the patient with the goal of developing a decision aid for patients. The decision aid would function as a tool to aid in shared decision making between patients and their physicians when considering treatment options that best reflects both medical evidence and individual patient’s values and needs for their care. The decision aid would also function to inform individuals of their treatment options, encourage engagement of patients in the treatment decision making process, and assist patients with processing their preferences so they can make choices that are reflective of their values. In order to determine how best to create such a tool it was first important to explore what motivated patients when choosing a particular therapy. Focus groups containing 5-7 parents of children (aged 1-22 years) with refractory ITP at any point in their life were conducted. During these focus groups open-ended questions were asked to guide the discussions. Following this, transcripts of the focus groups were analyzed for common themes that emerged from patients and key concepts were identified regarding why patients select a particular therapy. The major themes that emerged included experiences with treatment decision making such as differences in communication and adopting a “trial and error” approach to treatment, factors important in decision making such as quality of life, effectiveness, comfort, and degree of side effects, and the concept of remission which proved to hold different meanings to patients and clinicians. Clinicians’ views were not completely aligned with the patient experience and often parents felt like they were not critical decision-makers. Using this data, a decision-making aid can now be created.


Comments from PDSA’s Medical Advisors:

This is a useful and practical study exploring shared decision making with patients and their families. Key themes were identified that physicians and patients could focus on optimize treatment decisions. It emphasizes one of the current themes of ITP treatment (in both children and adults), which is to include the patient in deciding on management strategies. How this can be implemented in practice is a subject for future study.

Patient’s Reported Perceptions On Satisfaction with Immune Thrombocytopenia Treatments: Results from the ITP World Impact Survey (I-WISh)

doctor with clipboardIn this study, patients with immune thrombocytopenia (ITP) and their physicians report their perceptions towards available treatments (specifically corticosteroids, rituximab, and thrombopoietin receptor agonists), and their potential adverse events. In total, 1,507 ITP patients and 472 physicians (including many PDSA members) from across 13 different countries were provided surveys to fill out regarding their satisfaction with ITP related treatments. Most ITP patient participants (65%) were female, with an average age of 47 years.

Physicians were generally satisfied (75%) with treatment options available for ITP patients, and indicated that after a lack of efficacy (87%), side effects (76%) were the main reason for modifying treatment plans. When asked to provide their perceptions on common side effects of corticosteroids, rituximab, and TPO-RAs, there was some agreement among the steroid group particularly with regards to commonly reported symptoms such as corticosteroid induced weight gain, bloating, however, fatigue was reported as a side effect from the steroid by only 6% of physicians compared to 33% of patients. Fatigue (45%) and headache (24%) were the leading patient reported side effects with rituximab, however physicians focused more on infusion reactions (41%) and increased infections (32%). Patients reported more physical side effects such as body pains (23%) and fatigue (37%) as the most common adverse reactions associated with TPO-RA use, however physicians were more focused on the risks for selected thrombosis (24%), fatigue (22%), and nausea/vomiting (19%). When physicians were asked about patient communication, most felt they explained side effects risks prior to initiating treatment (94%), however only 72% of patients agreed with this. Most physicians felt they were up to date with therapy options (91%) however only 74% of patients agreed with this. In fact, 89% of physicians reported they kept their ITP patients informed about new therapy options, however only 61% of patients agreed with this.

Overall, patients were more satisfied with the effectiveness of rituximab and TPO-RAs than they were with corticosteroids. This is favorable since recommendations from the revised ASH Guidelines for ITP (2019) and the 2019 International Consensus Report support the earlier use of second line treatments, such as TPO-RAs, in management of patients. This approach would reduce the burden of steroid-induced side effects which in turn would improve the QoL of patients living with this rare disease.


Comments from PDSA’s Medical Advisors:

The primary manuscripts emerging from the I-WISh study were recently published in the American Journal of Hematology along with a commentary from Susan Mathias. This abstract illustrates the findings in one of the manuscripts and reflects how much information was obtained overall. Other parts are being analyzed and a second large I-WISh study is being initiated.

The results as presented highlight discrepancies between perceptions of patients and their physicians. On closer inspection, the perceptions of patients and physicians were reasonably well aligned. However, the study points out clearly that patients experienced fatigue and complained of other side effects more frequently than one might glean from physician response. It is important to point out that patients could tell their physicians “I feel fine” while complaining of fatigue when asked specifically. Thus, the discrepancy is not necessarily just “physician disregard” but also reflects how strongly patients discuss their symptoms and concerns to their physicians. The study thereby suggests areas in which specific questioning by health care providers is required to truly elucidate patients’ quality of life.


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