# Presentation: 675053

## Disclosures

- Disclosures

- Philip L. McCarthy Jr. BMT Program Roswell Park Cancer Institute, Buffalo, NY
- Participated in Dor Pharma acute Graft-versus-Host Disease (GvHD) Phase III study examining beclomethasone diproprionate (BDP)
- Involved in the design of future large chronic GvHD study
- Asked by BMC Communications Group, LLC if I would speak regarding the RPCI experience with BDP
- Paid for travel myself

## Investigational New Drug (IND) application for each patient and cross-referenced originally with Enteron IND
RPCI BMT program interest in BDP use long-term for chronic GvHD of the GI tract
Used BDP as capsule from Enteron as well as compounded in corn oil and later in capsules
BDP was used for the treatment of acute and chronic GI GvHD that was refractory to front line immunosuppressive therapy (calcineurin inhibitor and methylprednisolone 1-2 mg/kg/day or equivalent) or unable to wean or tolerate steroids without a GI GvHD flare
BDP used as a systemic “steroid-sparing” agent

**Iyer et al Long-Term Use of Oral Beclomethasone Dipropionate  (BDP) for the Treatment of Gastrointestinal (GI) Graft-versus-Host Disease (GvHD). *****Biology of Blood and Marrow Transplantation***** 11:587-592, 2005**
* *

- Investigational New Drug (IND) application for each patient and cross-referenced originally with Enteron IND
- RPCI BMT program interest in BDP use long-term for chronic GvHD of the GI tract
- Used BDP as capsule from Enteron as well as compounded in corn oil and later in capsules
- BDP was used for the treatment of acute and chronic GI GvHD that was refractory to front line immunosuppressive therapy (calcineurin inhibitor and methylprednisolone 1-2 mg/kg/day or equivalent) or unable to wean or tolerate steroids without a GI GvHD flare
- BDP used as a systemic “steroid-sparing” agent

## Patient Results, Iyer et al BBMT. 11:587-592, 2005

| Characteristic | Responders | Non-Responders |
| --- | --- | --- |
| Median Age (range) | 34 (5-51) | 46.5 (6-53) |
| Refractory GvHD |  |  |
| Acute | 0 | 2 |
| Chronic | 9 | 4 |
| BDP Start, Med (range) days after BMT  | 431 (265-1529) | 113 (39-251) |
| Med Steroid Dose at BDP start | 19 (0-88) | 113 (5-188) |
| # Cycles (range)
[28 days]  | 3 (1-20) | 2 (1-5) |

- Patient Results, Iyer et al ***BBMT. *****11:587-592, 2005**

## Patient Characteristics, Iyer et al BBMT. 11:587-592 (2005)

| Patient | Steroid Dose pre-BDP (mg/d Methylprednisolone  (MP) equiv) | Steroid Dose post-BDP (mg/d MP equiv) | % Change in Steroid Dose |
| --- | --- | --- | --- |
| 1 (CR) | 19  | 0 | -100 |
| 2 (CR) | 88 | 0 | -100 |
| 3 (CR) | 8 | 0 | -100 |
| 1 (PR) | 25 | 5 | -79 |
| 2 (PR) | 10 | 10 | 0 |
| 3 (PR) | 30 | 0.5 | -98 |
| 4 (PR) | 0 | 0 | NA |
| 5 (PR) | 75 | 75 | 0 |
| 6 (PR) | 10 | 10 | 0 |
| 1 (NR) | 113 | 238 | +111 |
| 2 (NR) | 5 | 53 | +950 |
| 3 (NR) | 88 | 463 | +428 |
| 4 (NR) | 138 | 88 | -36 |
| 5 (NR) | 188 | 38 | -80 |
| 6 (NR) | 113 | 113 | 0 |

- Patient Characteristics, Iyer et al ***BBMT. *****11:587-592 (2005)**

## BDP use at RPCI

- Pharmacy-compounded at present
- We would prefer a standardized formulation that would allow for upper and lower GI tract exposure
- We have used BDP in over 30 GI GvHD patients with a response (decreased immunosuppression)  in approximately 60% of patients
- Well tolerated in long-term use
- BDP blunts ACTH stimulation test adrenal response but does not have the systemic effects of standard steroid therapy
- Is this due to the liver first pass effect with metabolites that do not result in symptomatic adrenal suppression?
- BDP is the only drug added to steroids for upfront therapy of acute GvHD that generates a superior outcome.  Most immunosuppressive drugs added to steroids result in worse or equivalent outcomes
- BDP is useful therapy for acute GvHD and potentially for chronic GI GvHD (to be studied)