# Presentation: 666759

## FDA ODACAML in Older Individuals

**Frederick R. Appelbaum, MD**
**May 5, 2005**

## Age-related Incidence of AML and ALL

## Performance Status and Age in AMLN = 437

| Age | Performance Status |  |  |  |
| --- | --- | --- | --- | --- |
|  | 0 | 1 | 2 | 3 |
| 56-60 | .28 | .49 | .11 | .8 |
| 61-65 | .27 | .42 | .17 | .12 |
| 66-70 | .26 | .48 | .19 | .13 |
| 71-75 | .23 | .49 | .16 | .11 |
| 76+ | .16 | .47 | .18 | .18 |

## Age, Performance Status and Early Death in AMLN = 437

| Performance Status | Death within 30 days
 56-60	 61-70	    71+ |  |  |
| --- | --- | --- | --- |
| 0 | 0% | 13% | 9% |
| 1 | 0% | 14% | 21% |
| 2 | 38% | 19% | 42% |
| 3 | 17% | 24% | 62% |

## Age, Performance Status and Early Death in AMLN = 437

**Death within 30 days**

**Age, Performance Status and ****Early Death in AML****N = 437**

**Age**

## Age, Performance Status and Complete Response Rate in AMLN = 437

| Performance | Complete Response |  |  |
| --- | --- | --- | --- |
| Status | 56-60 | 61-70 | +70 |
| 0 | 70% | 40% | 50% |
| 1 | 60% | 49% | 38% |
| 2 | 25% | 38% | 27% |
| 3 | 50% | 41% | 29% |

## AML in Older Patients

**More often preceded by myelodysplasia**
**Less proliferative**
**More frequently associated with unfavorable cytogenetics**
**Expresses multidrug resistance more often**

## Hematologic Values at Diagnosis

|  | Age |  |  |  |
| --- | --- | --- | --- | --- |
|  | < 56 | 56-65 | 66-75 | > 75 |
| N | 381 | 222 | 249 | 68 |
| Hgb | 9.1 | 9 | 9.1 | 9.2 |
| WBC | 17.7 | 13.7 | 10.0 | 12.7 |
| PLT | 49 | 49 | 61 | 58 |
| % blasts | 39 | 27 | 24 | 26 |

## Southwest Oncology Group Leukemia CommitteePercentage of Patients in Cytogenetic Risk Groupsby Age Category

## Cytogenetics by Age

|  | Age |  |  |  |  |
| --- | --- | --- | --- | --- | --- |
|  | < 56 | 56-65 | 66-75 | > 75 | p |
| -5 or 5q (%) | 6 | 15 | 14 | 26 | <.0001 |
| -7 or 7q | 8 | 19 | 18 | 22 | <.0001 |
| 17p | 2 | 9 | 7 | 11 | =.0001 |
| t(8;21) | 7 | 4 | 2 | 0 | =.0087 |
| inv(16) | 9 | 2 | 4 | 7 | =.0011 |

## MRK Staining

|  | Age |  |  |  |
| --- | --- | --- | --- | --- |
|  | < 56 | 56-65 | 66-75 | > 75 |
| MRK+ (%) | 33 | 62 | 61 | 57 |

## Complete Response in Older AML Patients1

| Feature | N | CR% | p (univariate) |
| --- | --- | --- | --- |
| AML onset |  |  |  |
| 	2° | 50 | 24 | .0005 |
| 	1° | 161 | 52 |  |
| CD34 expression |  |  |  |
| 	+ | 138 | 38 | .0027 |
| 	- | 66 | 59 |  |
| MRK16 |  |  |  |
| 	Bright | 102 | 34 | .0019 |
| 	Dim | 33 | 45 |  |
| 	Negative | 54 | 67 |  |
| Cytogenetics |  |  |  |
| 	Unfavorable | 52 | 21 | < .0001 |
| 	Other | 112 | 55 |  |
| Functional Efflux |  |  |  |
| 	Positive | 101 | 35 | .0039 |
| 	Negative | 74 | 58 |  |

- 1Leith et al. Blood, 89:3323-3329, 1997

## Factors Associated with Lower CR Rates in Older AML Patients (multivariate)1N =211

| Factor | p value |
| --- | --- |
| 2°AML | .0035 |
| Unfavorable cytogenetics | .0031 |
| MDR1 expression | .0041 |

**Patients with all three factors had a CR rate of 11% versus a CR rate of 81% in patients without all three.**

**1****Leith et al., Blood 89: 3323-3329, 1997**

## MCR AML 111

**Induction ****	****– DAT vs. ADE vs. MAC**
**	****	****	****	****± G-CSF**
**Consolidation****	**** ****– ****2 cycles vs. 6 cycles**

**1****Goldstone et al., Blood 98: 1302, 2001**

## MRC AML 11

| N | 1314 |
| --- | --- |
| Age | 56-91 |
| AML onset |  |
| 	de novo | 81% |
| 	2° | 15% |
| 	treatment related | 4% |

## MRC AML 11Outcome

| CR | 62% |
| --- | --- |
| Death in CR | 7% |
| Relapse risk | 78% |
| DFS at 5 years | 15% |

## Survival on MRC AML 11 by Induction Treatment

## Factors Predictive of Outcome in Multivariate Analysis from MRC AML 11

| Parameter | Endpoint |  |
| --- | --- | --- |
|  | CR | OS |
| Cytogenetics | 2 x 10-14 | 8 x 10-11 |
| WBC | 4 x 10-6 | 6 x 10-13 |
| Age | 2 x 10-5 | 1 x 10-4 |
| 2° | 5 x 10-7 | 1 x 10-6 |
| Performance status | 3 x 10-4 | 2 x 10-6 |

## Summary

**Using conventional chemotherapy, complete response rates of 50% and a median survival of 9 months can be expected in patients over age 55 with AML.**
**However, patient and disease-related factors vary greatly and heavily influence treatment outcome. Particularly important are:**
**	****	****	****Age**
**	****	****	****Performance status**
**	****	****	****1****° vs. 2° presentation**
**	****	****	****Cytogenetics**
**	****	****	****MDR status**