Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation

Abstract

Corticosteroid-refractory graft-versus-host disease (SR-GVHD) remains a significant source of morbidity after allogeneic hematopoietic cell transplantation. No standard therapy exists in this setting; however, recent studies have demonstrated a very promising role for ruxolitinib, an oral Janus kinase 1/2 inhibitor. With increasing evidence of efficacy for SR-GVHD, limited data exist describing complications of ruxolitinib use, specifically infectious complications during use in SR-GVHD. In this study we report outcomes and infectious complications at our institution with ruxolitinib use. Overall, 43 patients were treated with ruxolitinib for SR-GVHD, 19 for acute SR-GVHD and 24 for chronic SR-GVHD. With respect to acute SR-GVHD, 15 patients had grade III acute GVHD and 4 patients had grade IV acute GVHD. At 28 days, a response rate of 84% was detected. With respect to chronic SR-GVHD, 16 patients had moderate refractory disease and 8 had severe refractory disease. At around 28 days, a 63% response rate was detected. Overall, 42% of patients (n = 18) treated with ruxolitinib had a documented infectious event. Infectious events were significantly more common among patients treated for acute SR-GVHD (P < .005). Among patients treated for acute SR-GVHD, both viral (n = 11) and bacterial (n = 10) events were frequently encountered. Cytomegalovirus reactivation was detected in 4 patients without organ involvement in any patient. Bacteremia was the most common bacterial event (n = 8), and 2 patients died after development of bacteremia. Only 5 of 24 patients treated with ruxolitinib for chronic SR-GVHD developed infectious complications after initiation of therapy. Nearly an even number of viral (n = 3) and bacterial (n = 4) were detected. This study supports the use of ruxolitinib in SR-GVHD, with impressive responses observed in both acute and chronic SR-GVHD. Infectious complications were particularly frequent among patients treated for acute SR-GVHD, and nearly all these patients were concurrently on high-dose steroids while on ruxolitinib. This study suggests careful monitoring for viral reactivation is required for patients initiated on ruxolitinib, supports the role of continuing prophylactic antimicrobial measures in ruxolitinib-treated GVHD patients, and raises the question of whether bacterial prophylaxis should be considered among patients initiated on ruxolitinib for acute SR-GVHD, particularly while on high-dose steroids.

Norovirus Replication in Human Intestinal Epithelial Cells Is Restricted by the Interferon-Induced JAK/STAT Signaling Pathway and RNA Polymerase II-Mediated Transcriptional Responses

“…Such infections have a profound impact on the overall health of the affected patient, resulting in significant weight loss and a requirement for enhanced nutritional support (84). Ruxolitinib (Jakavi) is approved for the treatment of a range of diseases, including splenomegaly, in patients with myelofibrosis and has been shown to be effective in the treatment of both the chronic and acute forms of the disease (38,85). Our data might suggest that the sustained administration of Rux in patients where chronic norovirus infection has been detected may exacerbate the disease.…”

Ruxolitinib salvage therapy is effective for steroid‐refractory graft‐versus‐host disease in children: A single‐center experience

“…Ruxolitinib is of interest in this respect, as it selectively inhibits the JAK‐STAT pathway. Murine models and adult clinical trials have demonstrated its significant benefit in the salvage therapy of steroid‐refractory GVHD . Although publications on the efficacy of ruxolitinib in adult patients with GVHD have been increasing, studies on children are relatively few …”

“…Murine models and adult clinical trials have demonstrated its significant benefit in the salvage therapy of steroid-refractory GVHD. [3][4][5] Although publications on the efficacy of ruxolitinib in adult patients with GVHD have been increasing, studies on children are relatively few. [6][7][8] Therefore, this study aimed to evaluate ruxolitinib efficacy in children with steroid-refractory acute GVHD (aGVHD) or chronic GVHD (cGVHD).…”

<p>Tuberculosis Peritonitis During Treatment of Polycythemia Vera with Ruxolitinib</p>

“…7,8 During ruxolitinib treatment, MPN cases may be complicated by opportunistic infections such as MTB and AMI, [9][10][11][12][13][14][15][16][17] pneumocystis jiroveci pneumonitis, 22 toxoplasma retinitis, 23 Cryptococcus neoformans pneumonitis, 24 and progressive multifocal leukoencephalopathy, 25 and by reactivation of latent viral infection with hepatitis B virus 26 and cytomegalovirus. 27 Thus, optimal anti-infective prophylaxis or monitoring for occult viral infection is needed with the use of ruxolitinib. 28 Our search of the English-written literature identified nine reports of MPN cases affected by MTB infection (Table 1).…”