Pat Killingsworth Pat Killingsworth

Impatient readers? I LOVE IT!

I love the fact that my email in-box is filling-up with notes from readers who are interested in specific poster and oral presentations from this year’s ASH!  Many of those interested are either in a specific study, or have friends or family that are involved in one of these clinical trials.

First, a confession.  Even an experienced ASH traveler like me can get overwhelmed by the size and scope of these meetings.  I’m not particularly organized, so it is easy for me to misplace notes I make on scraps of paper or somewhere buried on one of my three computers.

That said, I was able to follow-up on some of your requests.  So let’s get started!

OK , Terry, Suzie, Bill, Gary, Kathy and Sue.  About the Kyprolis/Rev/dex study,

Dr. Korde- Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone (CRd) in Newly Diagnosed Multiple Myeloma (MM) Patients

I was in the room most of the day.  It is part of a large ballroom on the top floor of the convention center.  Seats 600 or so.  This was one of the last presentations of the day, so attendance may have been down a bit.

Honestly, like most study results focusing on newly diagnosed patients, interest level may not have been as high as for some others.  This probably shocks those of you participating in the study, since for you there are few things more important these days, right?

Before I continue I want to commend you for diving-in and participating in a clinical study as important as this one–and for taking an intellectual interest in the process!  I personally know a half dozen patients involved in MLN9708 studies, 3 of them in my local support group.  I was tired and dragging, but I attended our December meeting last night.  Not a single question about their study.  All are just pleased to be doing well.  All three are watching their numbers go down.

But I want to be honest.  Not having remembered that this study was important to you, I sat working on posts involving other trial results from earlier in the day.  Like other trial results that I reviewed, I did note how well patients are responding: 40% CR, 33%VGPR, 20% PR and 6% SD.

I wasn’t focused-in-on the fact that the 6% SD was 1 patient in this very small study–a study that is so personal to several of you.  I hope none of you are that one patient–are you?

It isn’t unusual for many of these studies to have small sample sizes, another reason results sometimes don’t raise much interest.

One of my ongoing criticisms of these large conferences is how it’s all so impersonal, and everyone only focuses on the numbers.  I sometimes want to yell-out: These aren’t just numbers.  Each one represents a real patient with a family and friends who’s lives will never be the same!

How ironic that I would doing the same thing.  SORRY!  But there is a good reason why.  You need to understand that studies on newly diagnosed patients are the among the least watched category for multiple myeloma–except the the drug companies that have billions of dollars at stake.

Why?  Because we already have a half dozen drugs that work for newly diagnosed patients!  Think-back to a post I wrote a few days back about how Dr. Rajkumar prescribing the same Rev/dex combo I was given almost six years ago.  And it works, right?  And I will readily admit that because I was diagnosed back then, I’m more interested in therapies that will help heavily pretreated patients like me.  But I’m not alone.  Imagine being a myeloma doc who has to look one of his or her patients in the eyes and tell them there isn’t anything more they can do for them.  That’s what these clinicians are focused-on; finding hope for those of us who desperately need hope.

That said, Dr. Korde’s study is vitally important!  Not so much because it uses Kyprolis, but because it focuses on using the latest diagnostic and imaging techniques to see if there is a correlation between labs and diagnostics.  In other words, can “extreme” diagnostics predict how well patients will do when using this–or ultimately other–therapy combinations.

But with the NCI involved, I shouldn’t be surprised.  The National Cancer Institute has limited resources and focuses on areas that they think will be most important in the future, not just over the next few years.

Pretty cool!

As a matter of fact, one of my fellow IMF bloggers, Jack Aiello, was just picked to join the board that helps make the decisions about which research should receive focus and funding.  That’s pretty cool, too!

I tried but couldn’t find a picture of Dr Korde to use here.  Email me one and I will be glad to post it–you must be very proud!

Moving on, a reader was interested in poster results of a study that their doctor, Elias J. Anaissie, was involved with.  I’m afraid that I’m 0-2, because I didn’t see this poster.  But here’s what’s on it, which is the next best thing:

3145 Weight Loss, CD-34 Cell Dose and Melphalan Dose More Than 5 Mg/Kg Independently Predicted Severe Complications in Patients with Myeloma Undergoing Transplant

Clinical Allogeneic and Autologous Transplantation – Results
Program: Oral and Poster Abstracts
Type: Poster
Session: 731. Clinical Allogeneic and Autologous Transplantation – Results: Poster II
Sunday, December 9, 2012, 6:00 PM-8:00 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)

Stephen Medlin, DO, FACP1, Stephen Erickson, Ph.D2* and Elias J. Anaissie, MD3

1Myeloma Institute for Research and Therapy, *now at the University of Cincinnati Cancer Institute, University of Arkansas Medical Sciences, Little Rock, AR
2Bioinformatics, Arkansas Childrens Hospital Research Institute, Little Rock, AR
3Myeloma Institute For Research and Therapy, *Now at the University of Cincinnati Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR

Melphalan-based autologous stem cell transplant (Mel-ASCT) is effective therapy for multiple myeloma but can be associated with significant morbidity and life threatening complications.  Developing pre-transplant predictors for severe complications is therefore of paramount importance.

Our objective was to identify independent predictors of severe complications following Mel-ASCT defined as hospitalizations for 7 or more days or death.

We reviewed the records of 190 patients with newly diagnosed multiple myeloma who underwent their first Mel-ASCT as part of our Total Therapy protocol (TT4).  The treatment protocol randomized patients with low risk myeloma to receive standard therapy according to the predecessor trial TT-3 trial, or less intense therapy (light arm).  Compared to the standard arm (TT4S), the light arm (TT4L) consisted of only one cycle of induction prior to Mel-ASCT compared to two for TT4S and reduced the melphalan dose to 140 mg/m2 for serum creatinine >3mg/dl.  The following baseline variables were examined: demographics, weight, CBC, pre-transplant albumin, renal and liver function tests, peripheral blood CD3 and CD4 counts, stem cell product CD34 dose, echocardiogram, pulmonary function tests and mg/kg melphalan dose received.  Univariate and multivariate analyses for outcome predictors were performed.

190 patients (96 TT4S and 94 on TT4L) underwent their first Mel-ASCT November 2008 through July 2011.  Median age was 58.2 years.  One hundred and sixteen patients were males.  Patients were followed up to 60 days post-transplant.

Severe complications for mortality occurred more commonly in the standard arm with 5 deaths than in the light arm with 1 death.   Severe complications requiring hospital admission for more than seven days developed in 18 patients.  Ten of these patients were in the standard arm and eight patients were in the light arm.

Predictors of unfavorable outcomes in the combined group by univariate analysis were weight loss greater than 5% during induction(p=0.0029), platelets less than 65 (p=0.0090), CD34 cells/kg (p=0.0429), Beta-2 microglobulin >3.5 (p=0.0054), high ALT (p=0.0456), low socioeconomic status (p=0.0050), and dose of melphalan greater than 5 mg of melphalan/kg (p=0.0346).

Only three of the variables in the univariate analysis were significant in the combined multivariate analysis.  These three variables are presented in the table below.

Combined
Risk Factor Parameter Estimate Standard Error p-value Adjusted Odds Ratio
Greater than 5% loss of body weight

1.666

 

0.522

 

0.001

 

5.29

 

Infusion of less than 3.5 x10⁶ CD-34 cells/kg

1.361

 

0.525

 

0.010

 

3.90

 

Melphalan dose of greater than 5 mg/kg

1.563

 

0.507

 

0.002

 

4.77

 

We conclude that melphalan dose greater than 5 mg/kg, infusion of less than 3.5x 106 CD34 cells/kg and greater than 5% loss of body weight during induction predict for severe complications during Mel-ASCT.  Reducing intensity of induction therapy appears to be associated with less severe complications during Mel-ASCT.

Disclosures: No relevant conflicts of interest to declare.

Next, one of our readers from “across the pond” was frustrated by the fact that using maintenance therapy following an auto SCT wasn’t available to patients in England.  I stopped Dr. Durie on his way out of the room on the last day of the conference and asked him about it.  I could tell he was in a hurry, but he was very kind and paused to answer my question.

Dr. Durie was familiar with the issue.  To paraphrase (I didn’t have a note pad), he revealed that Celgene is involved in ongoing negotiations with British officials to supplement costs for patients that use maintenance.  He did mention that he felt use of maintenance therapy might be capped at one year.

WHEW!  If I didn’t get to your cause or concern, please email me and I will do my best to get it done for you.

Tomorrow I will share a bit about how I’m doing following six grueling days on the road–and following Zometa, Velcade, Revlimid and dex therapy the afternoon after I returned.  HINT:  I’m not in a coma, because I was able to write this lengthy post.  Do I get a dispensation for any typos or inverted words you may find in my copy?

Feel good and keep smiling!  Pat