1 00:00:07,240 --> 00:00:11,280 Greetings and welcome to EHA Unplugged, the official podcast 2 00:00:11,280 --> 00:00:15,200 channel of the European Hematology Association EHA. 3 00:00:15,800 --> 00:00:18,920 This material is based on content provided by Beijing. 4 00:00:19,240 --> 00:00:22,640 It has been reviewed by EHA which founded, unbiased and 5 00:00:22,640 --> 00:00:26,280 aligned with EHA educational standards as well as reworked by 6 00:00:26,280 --> 00:00:29,360 EHA to create an effective educational experience. 7 00:00:30,600 --> 00:00:35,080 Going to be having a chat about some of the issues that actually 8 00:00:35,080 --> 00:00:41,560 affect our patients facing CLL. I'm Leslie Fallowfield. 9 00:00:41,560 --> 00:00:46,000 I'm a professor of Psycho oncology at Brighton and Sussex 10 00:00:46,000 --> 00:00:50,320 Medical School and. Yes, you might know me because 11 00:00:50,320 --> 00:00:54,480 I'm a spender. I'm I'm a hematologist from 12 00:00:54,480 --> 00:00:57,560 Munich. I'm happy to talk today with 13 00:00:57,560 --> 00:01:02,400 Leslie about the subject. I'm usually not trained in, but 14 00:01:02,880 --> 00:01:06,800 I think seeing patients, I think we, we, we can exchange some 15 00:01:06,800 --> 00:01:09,680 experiences. OK. 16 00:01:09,680 --> 00:01:13,560 So I guess what I'd like to start by asking you, Clemens, is 17 00:01:13,560 --> 00:01:17,040 some of the advances that have been made in treatment terms. 18 00:01:17,440 --> 00:01:20,720 So this changing landscape, I mean, what difference has that 19 00:01:20,720 --> 00:01:23,960 made to you when you're seeing patients compared to when you 20 00:01:23,960 --> 00:01:26,440 were a baby doctor? Yes, right. 21 00:01:26,440 --> 00:01:32,240 So starting in the sidel field in the, I would say late 90s, I 22 00:01:32,240 --> 00:01:37,280 think we were happy that we had a drug like fluid Arab being 23 00:01:37,280 --> 00:01:39,320 available. So the perineal locks came into 24 00:01:39,320 --> 00:01:43,320 the field and we are not even talking about chemotherapy at 25 00:01:43,320 --> 00:01:46,160 all. And so it's still questionable 26 00:01:46,160 --> 00:01:50,840 whether bendamustine a drug, for example, Kirsten Fischer and and 27 00:01:50,840 --> 00:01:56,160 myself like very much 15 years ago, it's questionable whether 28 00:01:56,160 --> 00:01:59,040 this drug is not using any damage at all. 29 00:01:59,040 --> 00:02:02,040 We've heard yesterday from a young guy from Barcelona that 30 00:02:02,520 --> 00:02:06,600 even we cannot use more than one of mutations using benamastin. 31 00:02:07,680 --> 00:02:09,840 And from the patient's side, I think it's important. 32 00:02:09,840 --> 00:02:15,440 Now when patients think we would treat their leukemia, they might 33 00:02:15,440 --> 00:02:19,520 have pictures in mind, you know, that this means staying on the 34 00:02:19,520 --> 00:02:24,560 warts, losing hairs and having a lot of MSS and nausea. 35 00:02:25,440 --> 00:02:29,640 And I think this is the first misunderstanding we have really 36 00:02:29,640 --> 00:02:32,040 to cope with. Great. 37 00:02:32,320 --> 00:02:36,640 So, I mean, I think it's fair to say that the sorts of things 38 00:02:36,640 --> 00:02:42,440 that might excite a clinical scientist can be less exciting 39 00:02:42,440 --> 00:02:45,920 to a patient initially experiencing this very 40 00:02:45,920 --> 00:02:50,920 frightening sort of diagnosis, especially because as we know, 41 00:02:50,920 --> 00:02:56,200 some of these patients might be fairly asymptomatic and it could 42 00:02:56,200 --> 00:02:59,560 even be diagnosed via a random blood test. 43 00:02:59,760 --> 00:03:02,400 So I wonder if I could talk to you a little bit about 44 00:03:03,120 --> 00:03:05,920 nomenclature, the words that we use. 45 00:03:05,920 --> 00:03:10,040 But one can only make a choice about things if you understand 46 00:03:10,040 --> 00:03:15,280 what the whose choices are. So I mean, it's pretty 47 00:03:15,280 --> 00:03:19,360 difficult, isn't it, for an anxious patient who's suddenly 48 00:03:19,360 --> 00:03:21,960 being told they've got a potentially life threatening 49 00:03:21,960 --> 00:03:26,560 disease to cope with these esoteric concepts and words. 50 00:03:26,640 --> 00:03:29,960 I can't pronounce things, let alone the names of the drugs. 51 00:03:30,160 --> 00:03:32,360 How do you cope with that? Yeah. 52 00:03:32,480 --> 00:03:36,520 I mean, it's getting very difficult even to remember all 53 00:03:36,520 --> 00:03:39,640 the names, to pronounce them correctly, especially to think 54 00:03:39,640 --> 00:03:43,400 about the patient having never had any contact with these kind 55 00:03:43,400 --> 00:03:47,480 of drugs. So we have to take some extra 56 00:03:47,480 --> 00:03:50,880 time. We have to write things on a 57 00:03:50,880 --> 00:03:54,160 sheet. I usually also use my laptop and 58 00:03:54,160 --> 00:03:57,880 show the names so they have the chance to read the names at 59 00:03:57,880 --> 00:04:00,840 least. But I think even before talking 60 00:04:00,840 --> 00:04:05,280 about a specific therapy, we tell patients they're for 61 00:04:05,280 --> 00:04:10,000 leukemia and it's an early stage and we sent them home. 62 00:04:10,400 --> 00:04:13,240 So the patient's leaving a door knowing he has a leukemia. 63 00:04:13,240 --> 00:04:18,680 And this is also, you know, a kind of excited, you think 64 00:04:18,680 --> 00:04:25,880 situation for the patient having sort of democlass swinging above 65 00:04:25,880 --> 00:04:28,960 her or him. And this has to be reflected 66 00:04:28,960 --> 00:04:31,760 also by the physician. You know that this is, we are 67 00:04:31,760 --> 00:04:34,600 happy telling them it's early stage for us. 68 00:04:34,600 --> 00:04:38,000 It's good news, but can still be bad news for the other side of 69 00:04:38,000 --> 00:04:39,840 the patient and. I think that's a really 70 00:04:39,840 --> 00:04:43,360 interesting issue, isn't it? Because if we think about all 71 00:04:43,360 --> 00:04:46,600 the public awareness campaigns that have gone on, I think the 72 00:04:46,600 --> 00:04:51,280 message for most of Western Europe at least has got through 73 00:04:51,280 --> 00:04:55,560 that if you find a symptom, go and report it early. 74 00:04:55,840 --> 00:05:00,640 And if you get early diagnosis, treatment will be initiated and 75 00:05:00,640 --> 00:05:05,320 you've got a prospect of cure. So this goes counter to 76 00:05:05,320 --> 00:05:10,080 everything people have heard. Hey, you've got leukemia. 77 00:05:10,480 --> 00:05:14,120 But guess what? We don't need to treat it yet. 78 00:05:15,200 --> 00:05:17,120 I. Mean it's it it. 79 00:05:17,120 --> 00:05:21,960 It seems counterintuitive and I wonder if there's ever a 80 00:05:21,960 --> 00:05:27,560 situation where a patient is so panicked by the fact that they 81 00:05:27,560 --> 00:05:30,760 have got this life threatening disease that some people might 82 00:05:30,760 --> 00:05:33,000 be tempted to treat a bit too early. 83 00:05:34,040 --> 00:05:36,080 Right. I mean, there are this this kind 84 00:05:36,080 --> 00:05:39,680 of temptation, isn't it, You know, the action mode I call it, 85 00:05:39,680 --> 00:05:44,280 you know, just doing something. Although we know also big tries 86 00:05:44,280 --> 00:05:48,520 CL12 try by Peter Langabins, for example, showing definitely 87 00:05:48,520 --> 00:05:53,840 there is no use even in high risk early CLL to treat. 88 00:05:54,280 --> 00:05:58,440 But it's also for a physician sometimes could be 89 00:05:58,440 --> 00:06:02,760 unsatisfactory to send out a patient without doing anything. 90 00:06:03,000 --> 00:06:06,120 This has to be learned. And so we have to take these 91 00:06:06,120 --> 00:06:09,920 kind of mental health issues very seriously. 92 00:06:10,480 --> 00:06:15,800 It should be said that in CLL there is not only a medical need 93 00:06:15,800 --> 00:06:17,680 for this kind of mental health issues. 94 00:06:17,680 --> 00:06:21,080 I think there's also a scientific gap. 95 00:06:21,520 --> 00:06:24,480 We know it from breast cancer, from prostate cancer. 96 00:06:25,200 --> 00:06:27,880 A recent trial in bladder cancer, for example, shows 97 00:06:27,880 --> 00:06:31,760 exactly we have in 31 percent of patients mental health issues, 98 00:06:32,240 --> 00:06:38,440 depression, anxiety, you know, fear to lose any, you know, also 99 00:06:38,640 --> 00:06:40,600 welfare issues, things like this. 100 00:06:41,800 --> 00:06:46,640 But there is no good signs in CLL so far. 101 00:06:46,640 --> 00:06:49,880 And this can impact also on the treatment outcome. 102 00:06:49,960 --> 00:06:55,200 There are data from other tries that it's not only the notation 103 00:06:55,200 --> 00:07:00,120 status, it's not only TP 53. These simple issues like 104 00:07:00,120 --> 00:07:04,960 depressive patients not taking a pill and we are using mostly 105 00:07:04,960 --> 00:07:09,800 pills, Benito CLEX, PTK inhibitors can negatively impact 106 00:07:09,800 --> 00:07:12,680 also on the outcome. So I think that's very important 107 00:07:12,680 --> 00:07:15,240 to, yes. Stress, maybe we can come back 108 00:07:15,240 --> 00:07:20,280 and talk about how well we do measure mental health issues in 109 00:07:20,280 --> 00:07:23,560 our patients in a bit, but I want to come back to this sort 110 00:07:23,560 --> 00:07:28,400 of like seemingly difficult concept for a patient to embrace 111 00:07:28,480 --> 00:07:32,320 race that yes, you've got life threatening disease, but the 112 00:07:32,320 --> 00:07:35,560 good news is we don't have to treat it. 113 00:07:36,000 --> 00:07:39,400 So what does that patient actually do? 114 00:07:40,760 --> 00:07:43,640 I'm sure all of you know the phrase of, you know, sort of 115 00:07:43,640 --> 00:07:46,400 it's not watch and wait, it's watch and worry. 116 00:07:46,760 --> 00:07:50,880 But I think we actually don't look at the personality 117 00:07:50,880 --> 00:07:56,000 characteristics of patients sufficiently to recognize how we 118 00:07:56,000 --> 00:07:59,520 have to potentially change the wording a bit. 119 00:07:59,920 --> 00:08:04,200 Because for some patients, when you tell them those sorts of 120 00:08:04,200 --> 00:08:07,880 things, they'll probably actually go away feeling 121 00:08:08,200 --> 00:08:12,560 perfectly happy about it. They're able to almost sort of 122 00:08:12,560 --> 00:08:18,440 ignore it, but I wonder how many fall into that category rather 123 00:08:18,440 --> 00:08:24,640 than becoming vigilant about every ache, pain, sore throat, 124 00:08:24,640 --> 00:08:29,280 lump or whatever. And worst of all, those patients 125 00:08:29,280 --> 00:08:33,159 who have an anxious predisposition anyway, a trait 126 00:08:33,159 --> 00:08:37,120 of being rather anxious, how many of those become hyper 127 00:08:37,120 --> 00:08:42,200 vigilant, constantly going to their primary care physician, 128 00:08:42,400 --> 00:08:45,320 reporting things? So I mean, how do we deal with 129 00:08:45,320 --> 00:08:49,200 that, first of all? I think there is a significant 130 00:08:49,200 --> 00:08:54,640 fraction, you know, just palpating lumps and bumps all 131 00:08:54,640 --> 00:08:56,840 the time. And we all know these extra 132 00:08:56,840 --> 00:09:00,600 sheets the patients are presenting to us with leukocyte 133 00:09:00,600 --> 00:09:04,080 counts and we are a little bit annoyed sometimes. 134 00:09:04,280 --> 00:09:11,760 But this seems to be just, you know, this is done by some 135 00:09:11,760 --> 00:09:16,040 patients that want to gain by doing this again, some 136 00:09:16,040 --> 00:09:19,760 self-control because they're losing control when we tell them 137 00:09:19,760 --> 00:09:22,240 something about a still early stage leukemia. 138 00:09:22,240 --> 00:09:25,840 But this is out of control. And I accept this for my 139 00:09:25,840 --> 00:09:30,680 patients because I know maybe this helps them to regain 140 00:09:30,680 --> 00:09:33,320 self-control. Although I'm as a physician, 141 00:09:33,320 --> 00:09:35,280 maybe sometimes a little bit annoyed, you know, because 142 00:09:35,280 --> 00:09:40,280 though it's useless whether you have 23,000 or 25,000 leukocytes 143 00:09:40,280 --> 00:09:44,080 2 weeks later. So, So what about now sort of 144 00:09:44,080 --> 00:09:48,000 coming on to, let's assume that the patient is going to receive 145 00:09:48,000 --> 00:09:51,800 some treatment, but that could be continuous or intermittent. 146 00:09:52,120 --> 00:09:56,040 Again, you've got a bit of a problem here depending on. 147 00:09:56,320 --> 00:10:00,760 I would suggest not just the characteristics of the disease, 148 00:10:01,040 --> 00:10:04,040 but the characteristics of the patient in how they can accept 149 00:10:04,040 --> 00:10:04,760 that. Yeah. 150 00:10:05,520 --> 00:10:09,880 I mean, we, we, we usually say a time limit therapy is an extra 151 00:10:09,880 --> 00:10:12,920 bonus point for the therapy. I mean, we all know that we have 152 00:10:12,920 --> 00:10:17,760 to to base a treatment decision on, you know, usually molecule 153 00:10:17,760 --> 00:10:21,800 features, IG3 stairs, TP3 stairs, things like this. 154 00:10:22,280 --> 00:10:26,320 In the end we make a choice, but there are patients that are very 155 00:10:26,320 --> 00:10:30,000 happy with time limit therapy knowing this will come to an end 156 00:10:30,000 --> 00:10:32,240 after 12-15 months, something like this. 157 00:10:33,120 --> 00:10:40,120 But also patients being on Vanobi for example, they are a 158 00:10:40,120 --> 00:10:43,400 little bit, there are some patients being horrified when 159 00:10:43,400 --> 00:10:47,600 you know the treatment comes to an end, whether they are safe 160 00:10:47,600 --> 00:10:52,080 enough. When we stop, then sometimes 161 00:10:52,080 --> 00:10:56,480 very peculiar things start that patients are asking for MID 162 00:10:56,480 --> 00:10:58,960 assessment. We again just heard this is 163 00:10:59,480 --> 00:11:02,760 usually not routine practice, but still they want to know 164 00:11:02,760 --> 00:11:08,120 exactly about their disease status MID assessment is asked 165 00:11:08,120 --> 00:11:12,120 for. And so this we try to convince 166 00:11:12,120 --> 00:11:15,160 them this is maybe not the routine practice and this is 167 00:11:15,160 --> 00:11:17,520 maybe useless within clinical trials. 168 00:11:17,520 --> 00:11:19,160 We do it, but all sort of clinical tries. 169 00:11:19,160 --> 00:11:21,800 It's it's it's all done. On the other hand, we know there 170 00:11:21,800 --> 00:11:24,120 are there are treatments, continuous treatments as you 171 00:11:24,120 --> 00:11:27,720 just mentioned. This is when I tell the patients 172 00:11:27,720 --> 00:11:33,360 you do take this pill lifelong. Lifelong always sounds 173 00:11:33,760 --> 00:11:38,120 frightening. I usually then say OK, an anti 174 00:11:38,120 --> 00:11:41,160 hypertensive drug you're also taking lifelong but you would 175 00:11:41,160 --> 00:11:43,760 not think about stopping a hypertensive pill. 176 00:11:44,080 --> 00:11:48,360 So try to make this kind of pictures or similarities in 177 00:11:48,360 --> 00:11:52,400 medicine so that patients accept this kind of treatment. 178 00:11:52,400 --> 00:11:56,400 Also, continuous treatment can be it's a safety pill. 179 00:11:56,680 --> 00:11:59,960 Let's put it this way, every day you know they are taking. 180 00:12:00,320 --> 00:12:04,600 This can also be can also gain or the patient can gain 181 00:12:04,600 --> 00:12:06,640 reassurance by taking a pill every day. 182 00:12:07,120 --> 00:12:10,000 Now that's an interesting sort of point really, isn't it? 183 00:12:10,000 --> 00:12:15,640 Because obviously anxiety that this disease might sort of kill 184 00:12:15,640 --> 00:12:21,280 me anytime soon is a psycho noxious experience for anyone. 185 00:12:21,920 --> 00:12:26,640 But there are better ways to treat anxiety than to put people 186 00:12:26,640 --> 00:12:31,680 on expensive drugs with potential side effects, aren't 187 00:12:31,680 --> 00:12:34,520 there? And I just wonder how many 188 00:12:34,520 --> 00:12:40,280 people have within their centers good well integrated 189 00:12:40,480 --> 00:12:44,400 psychological support services that patients ought to 190 00:12:44,400 --> 00:12:47,040 automatically be referred to, I would suggest. 191 00:12:48,280 --> 00:12:50,920 I think there is still a major lack. 192 00:12:51,440 --> 00:12:57,640 Also Germany that we routinely don't refer patients to 193 00:12:58,520 --> 00:13:02,680 psychology specialists. There are some patient advocate 194 00:13:02,880 --> 00:13:08,160 groups we and support groups. We just give addresses and we 195 00:13:08,160 --> 00:13:11,520 just send them there. But we have for psychology 196 00:13:11,520 --> 00:13:13,440 support, we have long waiting lists. 197 00:13:13,440 --> 00:13:17,920 Also I think this is still an unmet medical need. 198 00:13:17,920 --> 00:13:22,160 You know that we have to take these kind of disorders being 199 00:13:22,160 --> 00:13:27,360 induced by by the leukemia diagnosis, that this has to be 200 00:13:27,360 --> 00:13:32,200 covered also in a way by by good psychology support in the 201 00:13:32,200 --> 00:13:34,120 system. I mean, it's quite interesting 202 00:13:34,120 --> 00:13:37,160 really, isn't it, that I think some patients feel, you know, 203 00:13:37,160 --> 00:13:39,840 but I'm not mad. And I, I, that's why I think it 204 00:13:39,840 --> 00:13:43,960 should be integrated that this is an important part of care, 205 00:13:44,280 --> 00:13:48,240 because we are always dealing with uncertainty in this issue. 206 00:13:48,640 --> 00:13:53,920 And I think the general public actually do believe medicine to 207 00:13:53,920 --> 00:13:57,640 be much more of an exact science than it actually is. 208 00:13:57,880 --> 00:14:03,400 As we all know, facts are only sort of hypothesis that are 209 00:14:03,680 --> 00:14:09,040 either refined or supported by the latest research data. 210 00:14:09,400 --> 00:14:13,400 And trying to cope and deal with that, I think is pushy, 211 00:14:13,400 --> 00:14:15,800 difficult. And I'm going to tease you with 212 00:14:15,800 --> 00:14:18,320 another sort of thing about uncertainty. 213 00:14:18,320 --> 00:14:22,600 And that is there are quite a lot of data now coming in 214 00:14:22,600 --> 00:14:28,520 different areas showing that the tolerance of uncertainty of the 215 00:14:28,520 --> 00:14:33,840 clinician who is talking to the patient will also affect what 216 00:14:33,840 --> 00:14:37,320 the treatment decision is. Because if you as a doctor are 217 00:14:37,320 --> 00:14:41,280 highly intolerant of uncertainty, you're more likely 218 00:14:41,280 --> 00:14:44,880 to. But early on, I think provide 219 00:14:44,880 --> 00:14:47,600 more aggressive therapy, order up more tests. 220 00:14:48,080 --> 00:14:51,120 That's correct. I think we learned an expression 221 00:14:51,120 --> 00:14:55,240 during the COVID pandemic. This is resilience, right? 222 00:14:56,080 --> 00:15:02,680 And I think that this is also important on the physician side 223 00:15:03,120 --> 00:15:12,120 to gain resilience and this this can be trained and to, you know, 224 00:15:12,120 --> 00:15:17,320 just keep cool and bring the message to the patient, but not 225 00:15:18,120 --> 00:15:23,200 just getting nervous about the leukemia per SE and starting 226 00:15:23,760 --> 00:15:26,480 irrational treatments too early or things like this. 227 00:15:26,480 --> 00:15:29,040 So. Do you ever feel blamed by the 228 00:15:29,040 --> 00:15:33,640 patient if in fact you've reassured them and then the 229 00:15:33,880 --> 00:15:37,320 disease does? Yeah, I mean, also you have to 230 00:15:37,320 --> 00:15:41,760 be also resilient on this, you know, because as a physician, 231 00:15:42,320 --> 00:15:45,920 you might get blamed to be inactive and doing nothing. 232 00:15:46,400 --> 00:15:51,000 But it's a matter of convincing. I usually try to convince them, 233 00:15:51,040 --> 00:15:55,240 you know, there is no need because we know exactly you will 234 00:15:55,240 --> 00:15:58,000 not benefit when we start too early, we might even harm you. 235 00:15:58,640 --> 00:16:01,920 But this depends then also on the patient's side, you know, 236 00:16:02,000 --> 00:16:06,080 whether the patient is accepting this kind of scientific 237 00:16:06,080 --> 00:16:09,640 knowledge from the physician. So communication is really very 238 00:16:09,640 --> 00:16:13,120 important, isn't it? And I guess there's also a 239 00:16:13,160 --> 00:16:18,320 social legal moral imperative now to be more patient centered, 240 00:16:18,320 --> 00:16:22,360 to involve patients more in their decision making. 241 00:16:22,360 --> 00:16:26,240 But I guess I come back to where I started here, that it is 242 00:16:26,240 --> 00:16:31,160 phenomenally difficult to explain the rationale and logic 243 00:16:31,480 --> 00:16:35,960 for the sorts of treatment management policies that you 244 00:16:35,960 --> 00:16:39,440 feel from the data that we have are most appropriate. 245 00:16:40,080 --> 00:16:43,640 So trust in the doctor becomes vital. 246 00:16:43,640 --> 00:16:46,360 If a patient doesn't really understand things because the 247 00:16:46,360 --> 00:16:51,960 concepts are too difficult or challenging, trust in the doctor 248 00:16:51,960 --> 00:16:55,640 is important. And we know again that if the 249 00:16:55,840 --> 00:16:59,200 patient doesn't understand, if the patient actually doesn't 250 00:16:59,200 --> 00:17:02,240 trust the healthcare professionals advice, they're 251 00:17:02,240 --> 00:17:08,359 very easy prey for the purveyors of snake venom on doctor Google. 252 00:17:08,880 --> 00:17:12,599 Doctor Google will come up with all sorts of brilliant ways to 253 00:17:12,599 --> 00:17:15,079 treat CLL. Does that happen in your 254 00:17:15,079 --> 00:17:17,640 practice very often if you say I'm not going to treat. 255 00:17:18,000 --> 00:17:23,160 You yes, I mean, patients are also in the Internet screening 256 00:17:23,160 --> 00:17:28,600 for some interesting things and they might even find some, some 257 00:17:28,600 --> 00:17:32,080 things like, you know, drink a lot of green tea or things like 258 00:17:32,080 --> 00:17:35,000 this. And I when they asked, it was 259 00:17:35,000 --> 00:17:37,600 one of the frequent questions they asked me is can I do 260 00:17:37,640 --> 00:17:39,880 anything instead of just waiting? 261 00:17:39,880 --> 00:17:43,800 You know, are there any, you know, paramedical things, you 262 00:17:43,800 --> 00:17:46,240 know, paramedicine things I can take? 263 00:17:47,120 --> 00:17:49,840 So that's really good. So rather than waiting for 264 00:17:49,840 --> 00:17:54,040 something to happen, here are a few things proactively that will 265 00:17:54,040 --> 00:17:57,440 benefit you anyway, like exercise and diet and 266 00:17:57,440 --> 00:17:59,240 everything. Excellent. 267 00:17:59,880 --> 00:18:01,840 I'm very glad I'm not a hematologist. 268 00:18:01,840 --> 00:18:05,160 I just actually talk about how you should talk to patients 269 00:18:05,160 --> 00:18:07,720 about these things. But I would like to just step 270 00:18:07,720 --> 00:18:12,600 back again to look at what the levels of anxiety and depression 271 00:18:12,600 --> 00:18:17,120 in patients actually are. There aren't very good data in 272 00:18:17,120 --> 00:18:20,400 fact, in CLL. So any of you out there who are 273 00:18:20,400 --> 00:18:24,600 keen to do some good new projects, I think it's a really 274 00:18:24,600 --> 00:18:28,880 important area to research, particularly because anxiety and 275 00:18:28,880 --> 00:18:31,800 uncertainty, they're very sort of closely linked. 276 00:18:32,320 --> 00:18:35,800 There has been systematic reviews of the data that are out 277 00:18:35,800 --> 00:18:38,200 there. They're not desperately good 278 00:18:38,200 --> 00:18:41,160 because lots of people use different sorts of assessment 279 00:18:41,160 --> 00:18:44,040 measures. But what we do know is that 280 00:18:44,040 --> 00:18:49,120 anxiety is probably between 1/4 and 1/3 of patients that have 281 00:18:49,120 --> 00:18:52,800 measurable anxiety and that's whether they're on what watchful 282 00:18:52,800 --> 00:19:00,000 waiting or on treatment. But depression is about 25% 283 00:19:00,000 --> 00:19:03,800 significantly higher in the treatment group. 284 00:19:04,120 --> 00:19:08,720 Now this could of course be because patients actually who 285 00:19:08,880 --> 00:19:12,840 have to start treatment or further lines of therapy 286 00:19:13,360 --> 00:19:18,000 recognize that their disease is perhaps more serious. 287 00:19:18,600 --> 00:19:22,000 Now I know that there's some interesting work that's been 288 00:19:22,000 --> 00:19:27,040 going on looking at the molecular underpinnings that why 289 00:19:27,040 --> 00:19:30,240 we should really be measuring depression particularly. 290 00:19:32,200 --> 00:19:36,360 There's indeed some early work, and I know that many people are 291 00:19:36,360 --> 00:19:38,960 sitting in this audience being very interested also in 292 00:19:38,960 --> 00:19:42,320 molecular science. I'll just give you 3 examples. 293 00:19:42,320 --> 00:19:48,960 So we know for depression and bipolar disorders, there is a 294 00:19:48,960 --> 00:19:59,040 snip for BCL 2. So the snip Rs 956572 you can 295 00:19:59,040 --> 00:20:05,840 write this down is associated with an exchange or turbulences 296 00:20:05,840 --> 00:20:09,680 in the calcium household and this is associated with. 297 00:20:10,280 --> 00:20:13,400 Depression. So we all know that BCL 2 is one 298 00:20:13,400 --> 00:20:19,720 target in CLL and so it might be worthwhile also studying these 299 00:20:19,720 --> 00:20:22,680 effect. Second example, we know one of 300 00:20:22,680 --> 00:20:26,840 the classics in treatment of depression is lithium. 301 00:20:27,560 --> 00:20:30,880 Lithium increases the BCL 2 levels. 302 00:20:31,520 --> 00:20:37,200 So you might conclude blocking BCL 2 might do something else, 303 00:20:37,840 --> 00:20:43,280 decreasing BCL 2 levels that we know, but also might foster 304 00:20:43,280 --> 00:20:47,560 depressive episodes. And there are other genes, it's 305 00:20:47,720 --> 00:20:54,760 so-called BCL 2 associated ethanol gene, back BAG back one, 306 00:20:54,760 --> 00:20:57,240 back two. It's also associated with 307 00:20:57,240 --> 00:21:00,880 depression. And you don't have to be a super 308 00:21:00,880 --> 00:21:05,640 scientist in order to think that, you know, perturbating the 309 00:21:05,640 --> 00:21:08,480 BCO 2 pathway with our modern drugs. 310 00:21:08,880 --> 00:21:12,520 We might also impact on these kind of this case is a MAPP 311 00:21:12,520 --> 00:21:17,200 kinase, a social pathway that there can be something going 312 00:21:17,480 --> 00:21:22,200 well or wrong depends. But I think we have really to 313 00:21:22,200 --> 00:21:26,640 invest more science also in mental health issues. 314 00:21:26,640 --> 00:21:30,840 We could integrate this in randomized clinical trials to 315 00:21:30,840 --> 00:21:36,840 see whether we really decrease or increase depression disorders 316 00:21:37,200 --> 00:21:40,120 and we could even associate this with molecular markers. 317 00:21:40,120 --> 00:21:42,840 I think this is an interesting topic. 318 00:21:42,840 --> 00:21:48,800 There are in other fields of Cancer Research first tries 319 00:21:48,800 --> 00:21:52,720 investigating this and I would just, you know, just fuss a 320 00:21:52,720 --> 00:21:54,600 little bit. This should also be done in the 321 00:21:54,600 --> 00:21:56,680 CRFL. Absolutely. 322 00:21:56,680 --> 00:22:00,160 I think that's important. And I mean, anything that sort 323 00:22:00,160 --> 00:22:04,880 of effects or improves anxiety and depression can only be 324 00:22:04,880 --> 00:22:08,520 helpful on multiple terms, particularly, as you know, we're 325 00:22:08,520 --> 00:22:12,240 very triumphant about the fact that there's less need now for 326 00:22:12,440 --> 00:22:15,600 chemotherapy. But oral therapies, of course, 327 00:22:15,600 --> 00:22:18,400 do depend on patients taking the pills. 328 00:22:18,400 --> 00:22:22,680 And depressive patients often don't take them. 329 00:22:22,720 --> 00:22:25,400 They don't adhere. So if we can sort of like 330 00:22:25,400 --> 00:22:28,720 summarize some of this, I mean, we could have probably stayed 331 00:22:28,720 --> 00:22:32,360 here all day talking about these things, but I think sort of the 332 00:22:32,360 --> 00:22:37,720 communication side really needs sort of addressing properly and 333 00:22:37,720 --> 00:22:41,160 thoroughly. 1 needs to be empathic and understanding, 334 00:22:41,160 --> 00:22:44,800 which I'm sure you are. But also there isn't like one 335 00:22:44,800 --> 00:22:49,840 set patter that is going to actually fit all patients given 336 00:22:49,840 --> 00:22:54,040 their underlying and pre-existing personality 337 00:22:54,040 --> 00:22:57,720 predispositions. I think being honest is 338 00:22:57,720 --> 00:23:03,160 important, but that demands also offering reassurance and 339 00:23:03,160 --> 00:23:05,440 thinking about the words being used. 340 00:23:05,480 --> 00:23:08,840 You know, I think we should get rid of a watchful waiting for a 341 00:23:08,840 --> 00:23:10,680 start. You're doing active 342 00:23:10,680 --> 00:23:14,320 surveillance. That sounds much more positive 343 00:23:14,320 --> 00:23:18,600 to the patients, but also sort of I think reducing the 344 00:23:18,600 --> 00:23:23,680 patient's uncertainty can only be achieved by sort of probably 345 00:23:23,680 --> 00:23:26,800 again, saying, you know, honestly, honestly, honestly, we 346 00:23:26,800 --> 00:23:30,840 don't want to start treatment until we feel it will genuinely 347 00:23:30,840 --> 00:23:33,680 benefit you. And that's why we will be 348 00:23:33,680 --> 00:23:36,360 measuring things. You don't have to keep on 349 00:23:36,360 --> 00:23:40,040 checking every few hours whether you've got a lump or a sore 350 00:23:40,040 --> 00:23:43,560 throat or whatever. So I wonder if there's anything 351 00:23:43,560 --> 00:23:47,120 you'd like to sort of add to Clemens about what you feel 352 00:23:47,400 --> 00:23:50,560 particularly for maybe younger people who haven't got a lot of 353 00:23:50,560 --> 00:23:53,440 experience in dealing with this concept? 354 00:23:53,920 --> 00:23:57,120 I think it's also the wording very, very important. 355 00:23:57,120 --> 00:23:59,440 So I also never say watch and wait. 356 00:23:59,640 --> 00:24:02,800 I always say watch and live. That's my my expression. 357 00:24:03,400 --> 00:24:07,160 I always say to the patients, you know, if you have questions 358 00:24:07,160 --> 00:24:10,120 after we've talked because questions come later, just give 359 00:24:10,120 --> 00:24:14,760 me a call or just come back to the office to get this kind of, 360 00:24:14,760 --> 00:24:17,800 you know, feedback loop and reassurance on the patient's 361 00:24:17,800 --> 00:24:19,840 side. And I think actually there's 362 00:24:19,840 --> 00:24:23,240 just one little thing I'd add to that also is that I think it's 363 00:24:23,240 --> 00:24:28,760 always worthwhile checking online what the charities, what 364 00:24:28,760 --> 00:24:33,160 are the things your patients are looking at because very often 365 00:24:33,480 --> 00:24:36,840 these don't, they show concordance with what you're 366 00:24:36,840 --> 00:24:40,040 saying and that will increase uncertainty even more.