Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.

     

Five Percent Lidocaine Cream Applied Simultaneously to the Skin and Mucosa of the Lips Creates Excellent Anesthesia for Filler Injections

Background. Injection of filler substances into the lips is painful, and many patients also find the injection of local or regional anesthesia into the lips painful.
Objective. To develop a highly effective and painless form of anesthesia to facilitate injection of filler substances into the lips.
Methods. Five percent lidocaine cream was applied simultaneously to the skin, vermilion, and mucosa of the lips (with the use of a barrier to keep the cream in contact with the mucosa and out of the rest of the mouth) for 20 to 30 minutes.
Results. Profound anesthesia of the lips was reliably produced, with no complications.
Conclusions. This "anesthetic cream block" is easier to perform and better tolerated than injectable anesthetics. Use of this technique is likely to expand the range of physicians who perform filler injections on the lips and will probably also expand the range of patients who wish to have filler injections done on their lips and who (because they had little or no discomfort) are willing to return for additional filler injections in the future.     

Cutis Marmorata Telangiectatica Congenita Associated with a Double Aortic Arch

Abstract: We report a patient with cutis marmorata telangiectatica with the hitherto unreported anomaly of a double aortic arch. The presence of two major vascular anomalies in this patient may be secondary to a developmental defect of the mesoderm during embryogenesis.     

"Are You Talking to Me?" Confronting Behavioral Disturbances in Patients With Headache

The famous question, "Are you talking to me?," was coined by Robert DeNiro in his lead role as Travis Bickle in the Martin Scorsese classic, Taxi Driver . The phrase also characterizes the troubling encounters that many headache-treating professionals confront as they attempt to discuss serious matters of care and compliance with some of their headache patients. Although most headache patients are eager to take professional advice and guidance, there exists a minority of patients whose behavior undermines a collaborative relationship between doctor and patient. In these cases, the physician may need to directly confront this behavior in order to overcome behavioral barriers that interfere with desirable treatment outcomes. This article offers explicit means and strategies to engage difficult patients, increase the likelihood of program adherence and improvement, and develop a more satisfying doctor-patient relationship, based on clinical experience in a national referral center for difficult-to-manage headache patients.